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Lu G, Wang Y, Huang H, Hua HL, Xi Y, Chen SM, Kong YG, Xu Y, Deng YQ, Tao ZZ. Association Between Diabetes Mellitus and Allergic Diseases Sensitized by Different Allergens and the Potential Mechanism of Diabetes Mellitus Affecting Ovalbumin-Induced Allergic Rhinitis. Am J Rhinol Allergy 2025:19458924251332786. [PMID: 40289517 DOI: 10.1177/19458924251332786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
ObjectiveTo investigate the association between diabetes mellitus (DM) and allergic diseases caused by different allergens and explore the mechanism of DM in allergic rhinitis (AR) induced by ovalbumin (OVA).MethodsWe established linear regression models to examine the correlation of specific immunoglobulin E (sIgE) and total immunoglobulin E (TIgE) with glycohemoglobin (A1c) and fasting plasma glucose (FPG) in individuals allergic to different allergens by retrospectively analyzing the 2005-2006 National Health and Nutrition Examination Survey database. Participants were classified into Allergy + DM and Allergy groups based on whether they had allergic disease and DM or only allergic disease. An AR mouse model was established using OVA. Mice were randomly assigned to the control, AR, diabetic (db), or db & AR group, with 6 mice in each group. The expression of GATA3, T-bet, and Foxp3 was detected using immunofluorescence and western blotting. Cytokines, FPG, A1c, and immunoglobulin in serum were detected using enzyme-linked immunosorbent assays.ResultsBased on the database, the TIgE and SIgE levels in participants with perennial allergies were lower in the Allergy + DM group than in the Allergy group, whereas those in participants with food allergies were higher in the Allergy + DM group than in the Allergy group. TIgE was negatively correlated with FPG or A1c in participants with perennial allergies and positively correlated with FPG and A1c in participants with egg allergy (among food allergens). In mice, AR symptoms, eosinophilic infiltration, and OVA-induced IgE levels were more serious in the db & AR group than in the AR group. TIgE was positively correlated with FPG, and interleukin-2 (IL-2) was negatively correlated with FPG; this was most pronounced in db & AR mice. The expression of T-bet and Foxp3 in mice was negatively associated with A1c.ConclusionsThe effect of DM on allergic diseases is related to the type of allergen. Decreased IL-2, T-bet, and Foxp3 levels resulting from elevated FPG and A1c levels may be involved in the association between OVA-induced AR and DM.
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Affiliation(s)
- Gan Lu
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
| | - Yan Wang
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
| | - Huan Huang
- School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, P.R. China
| | - Hong-Li Hua
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
| | - Yang Xi
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
| | - Shi-Ming Chen
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
- Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China
| | - Yong-Gang Kong
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
| | - Yu Xu
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
- Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China
| | - Yu-Qin Deng
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
| | - Ze-Zhang Tao
- Department of Otolaryngology, Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, P.R. China
- Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China
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González-Pérez R, Poza-Guedes P, Figueiras-Rincón MA, Colque-Bayona M, Sánchez-Machín I. The Allergy Crossroads of Subtropical Regions: Mites, Crustaceans, and the Rise of Edible Insects. Nutrients 2025; 17:1405. [PMID: 40362713 PMCID: PMC12074518 DOI: 10.3390/nu17091405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 04/16/2025] [Accepted: 04/17/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Edible insects (EIs) are increasingly recognized as a sustainable protein source, yet concerns persist regarding allergic reactions, even in individuals without prior known consumption. This study examines the immune response profile in patients from a subtropical area to improve understanding of mite-related cross-reactivity and emerging food sensitizations. Methods: To assess sensitization to edible insects, we analyzed 634 patients from a tertiary care allergy institution with high perennial exposure to house dust mites and storage mites. Sensitization patterns were assessed using the ALEX²® MacroArray platform, a multiplex IgE diagnostic tool covering 282 allergens, including Locusta migratoria (Lm), Acheta domesticus (Ad), and T. molitor (Tm). Patients with IgE levels ≥0.3 kU/L were evaluated for cross-reactivity to both mite allergens and pan-allergens. Results: Of the 634 patients, 138 (21.76%) exhibited IgE sensitization to at least one EI extract. Tropomyosin was the most prevalent pan-allergen (63.76%), followed by troponin-C (28.98%) and arginine kinase (26.81%). Notably, 95.66% of EI-sensitized individuals also reacted to mite allergens. However, 23.18% lacked reactivity to common pan-allergens, suggesting alternative sensitization mechanisms. Conclusions: This investigation can highlight regional variations in EI sensitization, where high mite exposure in subtropical climates appears to influence IgE responses to insect proteins. The findings suggest that EI sensitization is not merely incidental but represents a distinct immunological phenomenon shaped by environmental factors and allergen cross-reactivity. Since the presence of food-specific IgE does not reliably indicate clinical allergy, and the lack of food challenge data constrains diagnostic certainty, acknowledging EI sensitization as a potential risk factor remains essential for ensuring food safety and protecting public health.
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Affiliation(s)
- Ruperto González-Pérez
- Allergy Department, Hospital Universitario de Canarias, 38320 Santa Cruz de Tenerife, Spain; (P.P.-G.); (M.A.F.-R.); (I.S.-M.)
- Severe Asthma Unit, Hospital Universitario de Canarias, 38320 Santa Cruz de Tenerife, Spain
- Instituto de Investigación Sanitaria de Canarias (IISC), 38320 Santa Cruz de Tenerife, Spain
| | - Paloma Poza-Guedes
- Allergy Department, Hospital Universitario de Canarias, 38320 Santa Cruz de Tenerife, Spain; (P.P.-G.); (M.A.F.-R.); (I.S.-M.)
- Severe Asthma Unit, Hospital Universitario de Canarias, 38320 Santa Cruz de Tenerife, Spain
- Instituto de Investigación Sanitaria de Canarias (IISC), 38320 Santa Cruz de Tenerife, Spain
| | - Manuel Alberto Figueiras-Rincón
- Allergy Department, Hospital Universitario de Canarias, 38320 Santa Cruz de Tenerife, Spain; (P.P.-G.); (M.A.F.-R.); (I.S.-M.)
| | | | - Inmaculada Sánchez-Machín
- Allergy Department, Hospital Universitario de Canarias, 38320 Santa Cruz de Tenerife, Spain; (P.P.-G.); (M.A.F.-R.); (I.S.-M.)
- Instituto de Investigación Sanitaria de Canarias (IISC), 38320 Santa Cruz de Tenerife, Spain
- Allergen Immunotherapy Unit, Hospital Universitario de Canarias, 38320 Santa Cruz de Tenerife, Spain
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Eid AH, S Zaki E, Sabry MO, El-Shiekh RA, Khalaf SS. Exploring the anti-anaphylaxis potential of natural products: A Review. Inflammopharmacology 2025:10.1007/s10787-025-01685-2. [PMID: 40106030 DOI: 10.1007/s10787-025-01685-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 02/10/2025] [Indexed: 03/22/2025]
Abstract
Allergies are a common health issue affecting many people around the world, especially in developed countries. They occur when the immune system overreacts to substances that are usually harmless. Some common allergic conditions include asthma, sinus infections, skin rashes, food allergies, hay fever, severe allergic reactions, eczema, swelling, and reactions to medications or insect stings. The causes of these allergies are complex and often linked to genetics, which can lead to heightened immune responses known as atopy. Throughout history, plant extracts have been used for various purposes, including medicine and food. In addition, their bioactive compounds show a wide range of beneficial effects, such as reducing allergic reactions, fighting oxidative stress, mast cell stabilizers, and lowering inflammation, highlighting their potential for treating various health conditions. Flavonoids and phenolic compounds are commonly used in anaphylaxis for their potent anti-inflammatory action. This review aims to promote the use of natural products as potential treatments for anaphylaxis. In addition, the discovery of new drugs derived from natural sources holds significant promise for the management of anaphylaxis.
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Affiliation(s)
- Aya H Eid
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | - Eman S Zaki
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
| | - Miral O Sabry
- Faculty of Science, National University of Singapore, Singapore, Singapore
- Institute of Manufacturing Technology (SIMTech), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - Riham A El-Shiekh
- Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
| | - Samar S Khalaf
- Biochemistry Department Faculty of Pharmacy, Heliopolis University, Cairo, Egypt
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Matricardi PM, van Hage M, Custovic A, Korosec P, Santos AF, Valenta R. Molecular allergy diagnosis enabling personalized medicine. J Allergy Clin Immunol 2025:S0091-6749(25)00065-X. [PMID: 39855360 DOI: 10.1016/j.jaci.2025.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 01/15/2025] [Accepted: 01/17/2025] [Indexed: 01/27/2025]
Abstract
Allergic patients are characterized by complex and patient-specific IgE sensitization profiles to various allergens, which are accompanied by different phenotypes of allergic disease. Molecular allergy diagnosis establishes the patient's IgE reactivity profile at a molecular allergen level and has moved allergology into the era of precision medicine. Molecular allergology started in the late 1980s with the isolation of the first allergen-encoding DNA sequences. Already in 2002, the first allergen microarrays were developed for the assessment of complex IgE sensitization patterns. Recombinant allergens are used for a precise definition of personal IgE reactivity profiles, identification of genuine IgE sensitization to allergen sources for refined prescription of allergen-specific immunotherapy and allergen avoidance diagnosis of co- versus cross-sensitization, epidemiologic studies, and prediction of symptoms, phenotypes, and development of allergic disease. For example, molecular IgE sensitization patterns associated with more severe respiratory allergies, severe food allergy, and allergy to honeybee or vespids are already established. The implementation of molecular allergy diagnosis into daily clinical practice requires continuous medical education and training doctors in molecular allergy diagnosis, and may be facilitated by clinical decision support systems such as diagnostic algorithms that may take advantage of artificial intelligence.
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Affiliation(s)
- Paolo Maria Matricardi
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Institute of Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany.
| | - Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Respiratory Medicine, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Adnan Custovic
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Peter Korosec
- University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia; Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| | - Alexandra F Santos
- Department of Women and Children's Health (Pediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom; Children's Allergy Service, Evelina Children's Hospital, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Rudolf Valenta
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Department of Clinical Immunology and Allergy, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russia; Karl Landsteiner University, Krems an der Donau, Austria; National Research Center, National Research Center Institute of Immunology Institute of Immunology, Federal Medical-Biological Agency of Russia, Moscow, Russia
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Koren A, Korosec P. Multiplex basophil activation tests for allergy diagnosis: present and future applications. FRONTIERS IN ALLERGY 2025; 5:1515843. [PMID: 39877248 PMCID: PMC11772483 DOI: 10.3389/falgy.2024.1515843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/24/2024] [Indexed: 01/31/2025] Open
Abstract
The basophil activation test (BAT) has become a major cellular in vitro test for evaluating the allergenic activity of specific IgEs. The impact of the BAT is due to the ability of blood basophil granulocytes to present IgE on the high-affinity FcεRI receptor and to mirror the mast cell response that elicits an acute allergic reaction. The BAT proved to be able to identify allergic patients at risk of reacting to a low dose of the allergen and/or developing life-threatening reactions and thus can significantly improve the current management of allergic patients. However, to improve the diagnostic utility for identifying the allergenic activity of different genuinely sensitizing allergens and lower the procedure and labour requirements, developing a multiplex BAT approach incorporating multiple allergen components would be highly anticipated. Recently, the novel multiplex BAT was described utilizing two major innovative steps. The first step was the fluorescent labeling of allergens. The second step was applying fluorescently labeled allergens in flow cytometry assessment to analyze the activation of basophil subpopulations gated according to the binding of different allergens or to evaluate the fluorescence intensity of multiple allergens on the surface of basophils. These novel cellular multiplex approaches will advance our understanding of IgE-mediated responses. Integration of multiplex BAT, in addition to multiplex IgE assays into practice, will personalize the measurement of allergenic IgE activity and can help estimate the likelihood of clinical relevance and risks for multiple allergens when testing individual allergic patients.
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Affiliation(s)
- Ana Koren
- Laboratory for Clinical Immunology and Molecular Genetics, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia
| | - Peter Korosec
- Laboratory for Clinical Immunology and Molecular Genetics, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
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Hu H, Qin QZ, Zheng W, Xu ZQ, Chen X. Construction of a Hybrid Vaccine Based on Der f 35-Derived Peptides with Reduced Allergenicity. Int Arch Allergy Immunol 2024; 186:401-417. [PMID: 39591953 DOI: 10.1159/000541815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 10/03/2024] [Indexed: 11/28/2024] Open
Abstract
INTRODUCTION House dust mite is the primary trigger of allergic respiratory diseases worldwide, and allergen-specific immunotherapy (AIT) is the only disease-modifying treatment in the clinic. The use of allergen molecules instead of extracts is a promising strategy in AIT. In this study, we constructed a peptide hybrid vaccine against the major mite allergen Der f 35 and verified its hypoallergenicity, making it to be a promising candidate for AIT of mite allergy. METHODS The gene encoding Der f 35 was retrieved and synthesized. The hypoallergenic peptide fragments derived from the B-cell epitopes were synthesized based on the predicted profiles of B-cell or T helper-cell epitopes in Der f 35, they were verified by immunoglobulin E (IgE)-reaction test and fused to non-allergenic protein carrier to form the hybrid vaccine. Both the wild-type Der f 35 and the designed vaccine were expressed in Escherichia coli and purified by chromatography; their IgE-binding activity was compared by indirect enzyme-linked immunosorbent assay (ELISA), Western blot, inhibition ELISA, and basophil activation test (BAT). The blocking immunoglobulin G (IgG) against the designed vaccine was raised in rabbits and its ability to inhibit IgE binding of Der f 35 was evaluated by ELISA. The vaccine's effects on peripheral blood mononuclear cells (PBMCs) were investigated. RESULTS A total of 29 out of 60 (48.33%) IgE-positive sera against Der f 35 were screened. Five peptide fragments (residue 39-42, 60-67, 73-107, 111-118, 126-143) from Der f 35 were selected as candidates, in which four peptides exhibited almost no IgE reactivity and the fragment 73-107 had weak reactions. Only 5.98-24.02% inhibition rates could be achieved by the peptides when compared with Der f 35 (97.32%). The designed vaccine migrated at approximately 30 kDa by SDS-PAGE. The IgE-ELISA revealed a significant reduction in IgE-binding activity to the vaccine when compared to wild-type Der f 35 (p < 0.0001); the decreased allergenicity was further confirmed by IgE-Western blot, inhibition ELISA, and BAT, respectively. The IgE-reactivity of Der f 35 could be blocked by the vaccine-induced IgG (p < 0.01). The levels of IL-5 and IL-13 from PBMCs were significantly decreased after stimulation by the vaccine than that by Der f 35 (p < 0.05). CONCLUSION The designed B-cell epitope vaccine of Der f 35 showed greatly diminished allergenicity and Th2 activity. It could be an effective and safe candidate to prevent allergic adverse reactions during the immunotherapy of mite allergy and merits the further study.
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Affiliation(s)
- Haoyang Hu
- School of Medicine, Nantong University, Nantong, China
| | - Qiao-Zhi Qin
- Pediatric Department, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Wei Zheng
- Department of Pharmacy, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Zhi-Qiang Xu
- Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiang Chen
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, China
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Wang B, Zhang D, Jiang Z, Liu F. Analysis of allergen positivity rates in relation to gender, age, and cross-reactivity patterns. Sci Rep 2024; 14:27840. [PMID: 39537696 PMCID: PMC11561105 DOI: 10.1038/s41598-024-78909-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024] Open
Abstract
OBJECTIVE This study aims to gain a deeper understanding of the patterns of allergen detection positivity rates among different age and gender groups, and to explore cross-reactivity patterns among allergens. METHODS We conducted a retrospective analysis of patients who underwent allergen testing at our hospital. The sample for this study included all patients who underwent allergen testing. We utilized immune blotting to detect specific IgE antibodies to 20 allergens in patient sera. RESULTS The study results showed a higher proportion of female samples (72.35%) compared to male samples (27.65%). Among all participants, the age distribution was primarily concentrated in the 25-35 age group, accounting for 37.43% of the total sample, followed by the 45 years and older age group, accounting for 27.00%. This indicates that allergic symptoms may occur not only in children and adolescents but also at any time after adulthood. We further observed significant influences of factors such as gender and age on individual sensitivity to specific allergens. For example, compared to males, females were found to be more sensitive to certain allergens such as cat hair, dust mites, and dog epithelium. Similarly, we also found variations in sensitivity to specific allergens among different age groups. CONCLUSION Close monitoring of allergen distribution in populations facilitates active engagement of allergic individuals in self-management, while gender and age may be important factors influencing individual sensitivity to specific allergens. These findings provide valuable insights for understanding the pathogenesis of allergic diseases and designing more effective prevention and treatment strategies.
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Affiliation(s)
- Ben Wang
- Department of Dermatology, Beijing Chao-yang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, China
| | - Di Zhang
- Department of Dermatology, Beijing Chao-yang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, China
| | - Zhihui Jiang
- Department of Dermatology, Beijing Chao-yang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, China
| | - Fang Liu
- Department of Dermatology, Beijing Chao-yang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, China.
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Baba SM, Shafi T, Rasool R, Hameed A, Shafi S, Ahmad SF. Molecular investigation of vitamin D receptor (VDR) genetic variants and their impact on VDR mRNA and serum vitamin D levels in allergic rhinitis in an Indian population: A case-control study. Int J Immunogenet 2024; 51:300-309. [PMID: 38809236 DOI: 10.1111/iji.12679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 03/28/2024] [Accepted: 05/08/2024] [Indexed: 05/30/2024]
Abstract
Vitamin D deficiency is widespread and poses a significant health concern, as emerging research links it to allergic diseases owing to its immunomodulatory functions. The optimal functioning of vitamin D and its activation depend on its nuclear receptor, vitamin D receptor (VDR). Genetic variants of VDR have been explored as potential factors in autoimmune and allergic diseases, with limited studies on their association with allergic rhinitis (AR). The present investigation aims to analyse the role of three VDR genetic variants - TaqI, FokI and BsmI - in AR susceptibility and their impact on VDR mRNA and serum vitamin D levels. A total of 550 subjects, consisting of 250 AR cases and 300 age- and gender-matched controls, underwent genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). VDR mRNA and vitamin D levels were determined by quantitative real-time PCR and chemiluminescence, respectively. Although TaqI did not exhibit significant differences, FokI demonstrated a noteworthy association with AR, particularly with the CC genotype (odds ratio [OR]: 3.34; confidence interval [CI]: 1.79-6.23). Similarly, BsmI revealed an increased risk for AR, with the GA + AA genotypes showing a 2.2-fold elevated risk (OR: 2.20; CI: 1.53-3.16). VDR mRNA expression was threefold lower in AR patients (p < .0001), accompanied by reduced serum vitamin D levels (p < .0001). In addition, CC (p = .01) and AA (p = .02) genotypes of FokI and BsmI were associated with reduced VDR mRNA levels, whereas TaqI showed no such association. Similarly, heterozygous genotypes of TaqI and FokI, as well as homozygous AA of BsmI, correlated with lower serum vitamin D levels (p < .001). This study emphasizes the intricate relationship among VDR genetic variations, altered VDR activity, immune modulation and vitamin D metabolism in AR. Further research involving diverse populations is crucial for confirming and generalizing these findings, paving the way for personalized therapeutic interventions in vitamin D-related disorders.
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Affiliation(s)
- Shahid M Baba
- Centre for Vocational Studies, Islamic University of Science & Technology, Awantipora, Pulwama, Jammu and Kashmir, India
| | - Tabasum Shafi
- Department of Immunology & Molecular Medicine, SKIMS, Srinagar, Jammu and Kashmir, India
| | - Roohi Rasool
- Department of Immunology & Molecular Medicine, SKIMS, Srinagar, Jammu and Kashmir, India
| | - Afaq Hameed
- Department of Immunology & Molecular Medicine, SKIMS, Srinagar, Jammu and Kashmir, India
| | - Saba Shafi
- Department of Clinical Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India
| | - Sheikh F Ahmad
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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Zhao L, Ma T, Wang X, Wang H, Liu Y, Wu S, Fu L, Gilissen L, van Ree R, Wang X, Gao Z. Food-Pollen Cross-Reactivity and its Molecular Diagnosis in China. Curr Allergy Asthma Rep 2024; 24:497-508. [PMID: 38976200 DOI: 10.1007/s11882-024-01162-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2024] [Indexed: 07/09/2024]
Abstract
PURPOSE OF REVIEW Plant-derived foods are one of the most common causative sources of food allergy in China, with a significant relationship to pollinosis. This review aims to provide a comprehensive overview of this food-pollen allergy syndrome and its molecular allergen diagnosis to better understand the cross-reactive basis. RECENT FINDINGS Food-pollen cross-reactivity has been mainly reported in Northern China, Artemisia pollen is the major related inhalant source, followed by tree pollen (Betula), while grass pollen plays a minor role. Pollen allergy is relatively low in Southern China, with allergies to grass pollen being more important than weed and tree pollens. Rosaceae fruits and legume seeds stand out as major related allergenic foods. Non-specific lipid transfer protein (nsLTP) has been found to be the most clinically relevant cross-reacting allergenic component, able to induce severe reactions. PR-10, profilin, defensin, chitinase, and gibberellin-regulated proteins are other important cross-reactive allergen molecules. Artemisia pollen can induce allergenic cross-reactions with a wide range of plant-derived foods in China, and spring tree pollens (Betula) are also important. nsLTP found in both pollen and plant-derived food is considered the most significant allergen in food pollen cross-reactivity. Component-resolved diagnosis with potential allergenic proteins is recommended to improve diagnostic accuracy and predict the potential risk of causing allergic symptoms.
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Affiliation(s)
- Lan Zhao
- Allergy Research Center, Zhejiang University, Hangzhou, 310058, China
| | - Tingting Ma
- Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Xiaoyan Wang
- Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Hongtian Wang
- Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yi Liu
- Hangzhou Zheda Dixun Biological Gene Engineering Co. Ltd, Hangzhou, China
| | - Shandong Wu
- Hangzhou Zheda Dixun Biological Gene Engineering Co. Ltd, Hangzhou, China
| | - Linglin Fu
- School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310018, China
| | - Luud Gilissen
- Plant Breeding, Wageningen University & Research, Wageningen, The Netherlands
| | - Ronald van Ree
- Departments of Experimental Immunology and of Otorhinolaryngology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Xueyan Wang
- Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
| | - Zhongshan Gao
- Allergy Research Center, Zhejiang University, Hangzhou, 310058, China.
- Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
- Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
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Light SH, Nagler CR. Regulation of immune responses to food by commensal microbes. Immunol Rev 2024; 326:203-218. [PMID: 39285525 PMCID: PMC11472335 DOI: 10.1111/imr.13396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/28/2024]
Abstract
The increasing prevalence of immune-mediated non-communicable chronic diseases, such as food allergies, has prompted a deeper investigation into the role of the gut microbiome in modulating immune responses. Here, we explore the complex interactions between commensal microbes and the host immune system, highlighting the critical role of gut bacteria in maintaining immune homeostasis. We examine how modern lifestyle practices and environmental factors have disrupted co-evolved host-microbe interactions and discuss how changes in microbiome composition impact epithelial barrier function, responses to food allergens, and susceptibility to allergic diseases. Finally, we examine the potential of bioengineered microbiome-based therapies, and live biotherapeutic products, for reestablishing immune homeostasis to prevent or treat food allergies.
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Affiliation(s)
- Samuel H. Light
- Department of Microbiology, University of Chicago, Chicago IL, 60637
| | - Cathryn R. Nagler
- Department of Pathology, University of Chicago, Chicago IL, 60637
- Department of Biological Sciences Division, Pritzker School of Molecular Engineering, University of Chicago, Chicago IL, 60637
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Braun C, Badiou C, Guironnet-Paquet A, Iwata M, Lenief V, Mosnier A, Beauclair C, Renucci E, Bouschon P, Cuzin R, Briend Y, Patra V, Patot S, Scharschmidt TC, van Wamel W, Lemmens N, Nakajima S, Vandenesh F, Nicolas JF, Lina G, Nosbaum A, Vocanson M. Staphylococcus aureus-specific skin resident memory T cells protect against bacteria colonization but exacerbate atopic dermatitis-like flares in mice. J Allergy Clin Immunol 2024; 154:355-374. [PMID: 38734386 DOI: 10.1016/j.jaci.2024.03.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 02/15/2024] [Accepted: 03/26/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND The contribution of Staphylococcus aureus to the exacerbation of atopic dermatitis (AD) is widely documented, but its role as a primary trigger of AD skin symptoms remains poorly explored. OBJECTIVES This study sought to reappraise the main bacterial factors and underlying immune mechanisms by which S aureus triggers AD-like inflammation. METHODS This study capitalized on a preclinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury. RESULTS The development of S aureus-induced dermatitis depended on the nature of the S aureus strain, its viability, the concentration of the applied bacterial suspension, the production of secreted and nonsecreted factors, as well as the activation of accessory gene regulatory quorum sensing system. In addition, the rising dermatitis, which exhibited the well-documented AD cytokine signature, was significantly inhibited in inflammasome adaptor apoptosis-associated speck-like protein containing a CARD domain- and monocyte/macrophage-deficient animals, but not in T- and B-cell-deficient mice, suggesting a major role for the innate response in the induction of skin inflammation. However, bacterial exposure generated a robust adaptive immune response against S aureus, and an accumulation of S aureus-specific γδ and CD4+ tissue resident memory T cells at the site of previous dermatitis. The latter both contributed to worsen the flares of AD-like dermatitis on new bacteria exposures, but also, protected the mice from persistent bacterial colonization. CONCLUSIONS These data highlight the induction of unique AD-like inflammation, with the generation of proinflammatory but protective tissue resident memory T cells in a context of natural exposure to pathogenic S aureus strains.
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Affiliation(s)
- Camille Braun
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France; Service de Pédiatrie, Pneumologie, Allergologie, Mucoviscidose, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
| | - Cédric Badiou
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Aurélie Guironnet-Paquet
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France; Etablissement Français du Sang Auvergne Rhône-Alpes, Apheresis Unit, Hôpital Lyon Sud, Pierre-Bénite, France
| | - Masashi Iwata
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Vanina Lenief
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Amandine Mosnier
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Charlotte Beauclair
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Emilie Renucci
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Pauline Bouschon
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Roxane Cuzin
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Yoann Briend
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Vijaykumar Patra
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | - Sabine Patot
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France
| | | | - Willem van Wamel
- Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Nicole Lemmens
- Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Saeko Nakajima
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - François Vandenesh
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France; Service de Microbiologie Clinique, Groupement Hospitalier Nord, Hospices Civils de Lyon, Bron, France; Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France
| | - Jean-François Nicolas
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France; Service d'Allergologie et Immunologie Clinique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Gérard Lina
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France; Service de Microbiologie Clinique, Groupement Hospitalier Nord, Hospices Civils de Lyon, Bron, France; Centre National de Référence des Staphylocoques, Hospices Civils de Lyon, Lyon, France
| | - Audrey Nosbaum
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France; Service d'Allergologie et Immunologie Clinique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Marc Vocanson
- Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, Unité Mixte de Recherche 5308, Centre national de la recherche scientifique, Ecole Normale Supérieure de Lyon, Lyon, France.
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12
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Zettl I, Bauernfeind C, Kollárová J, Flicker S. Single-Domain Antibodies-Novel Tools to Study and Treat Allergies. Int J Mol Sci 2024; 25:7602. [PMID: 39062843 PMCID: PMC11277559 DOI: 10.3390/ijms25147602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 07/03/2024] [Accepted: 07/04/2024] [Indexed: 07/28/2024] Open
Abstract
IgE-mediated allergies represent a major health problem in the modern world. Apart from allergen-specific immunotherapy (AIT), the only disease-modifying treatment, researchers focus on biologics that target different key molecules such as allergens, IgE, or type 2 cytokines to ameliorate allergic symptoms. Single-domain antibodies, or nanobodies, are the newcomers in biotherapeutics, and their huge potential is being investigated in various research fields since their discovery 30 years ago. While they are dominantly applied for theranostics of cancer and treatment of infectious diseases, nanobodies have become increasingly substantial in allergology over the last decade. In this review, we discuss the prerequisites that we consider to be important for generating useful nanobody-based drug candidates for treating allergies. We further summarize the available research data on nanobodies used as allergen monitoring and detection probes and for therapeutic approaches. We reflect on the limitations that have to be addressed during the development process, such as in vivo half-life and immunogenicity. Finally, we speculate about novel application formats for allergy treatment that might be available in the future.
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Affiliation(s)
- Ines Zettl
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Clarissa Bauernfeind
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
- Center for Cancer Research, Medical University of Vienna, 1090 Vienna, Austria
| | - Jessica Kollárová
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Sabine Flicker
- Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
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13
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Kidane FA, Müller L, Rocha-Hasler M, Tu A, Stanek V, Campion N, Bartosik T, Zghaebi M, Stoshikj S, Gompelmann D, Spittler A, Idzko M, Eckl-Dorna J, Schneider S. Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry. Clin Immunol 2024; 262:110174. [PMID: 38462155 DOI: 10.1016/j.clim.2024.110174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 02/19/2024] [Accepted: 02/20/2024] [Indexed: 03/12/2024]
Abstract
Chronic rhinosinusitis (CRS) is a persistent nasal and paranasal sinus mucosa inflammation comprising two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drug (NSAID) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS frequently intertwines with respiratory allergies. This study investigated levels of 33 different nasal and serum cytokines and phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) within cohorts of CRS patients (n = 24), additionally examining the influence of comorbid respiratory allergies by mass cytometry. N-ERD patients showed heightened type 2 nasal cytokine levels. Mass cytometry revealed increased activated naive B cell levels in CRSwNP and N-ERD, while resting naive B cells were higher in CRSsNP. Th2a cell levels were significantly elevated in allergic subjects, but not in CRS groups. In conclusion, there are distinct immunological features in PBMCs of CRS phenotypes and allergy.
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Affiliation(s)
- Fana Alem Kidane
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Lena Müller
- Core Facilities, Medical University of Vienna, Vienna, Austria
| | | | - Aldine Tu
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Victoria Stanek
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Nicholas Campion
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Tina Bartosik
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Mohammed Zghaebi
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Slagjana Stoshikj
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Daniela Gompelmann
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Andreas Spittler
- Core Facilities, Medical University of Vienna, Vienna, Austria; Department of Surgery, Research Lab, Medical University of Vienna, Vienna, Austria
| | - Marco Idzko
- Division of Pulmonology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Julia Eckl-Dorna
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.
| | - Sven Schneider
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
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14
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Brazhnikov G, Smolnikov E, Litovkina A, Jiang T, Shatilov A, Tulaeva I, Tulaev M, Karaulov A, Poroshina A, Zhernov Y, Focke‐Tejkl M, Weber M, Akinfenwa O, Elisyutina O, Andreev S, Shilovskiy I, Shershakova N, Smirnov V, Fedenko E, Lepeshkova TS, Beltyukov EC, Naumova VV, Kundi M, Khaitov M, Wiedermann U, Valenta R, Campana R. Natural human Bet v 1-specific IgG antibodies recognize non-conformational epitopes whereas IgE reacts with conformational epitopes. Allergy 2023; 78:3136-3153. [PMID: 37701941 PMCID: PMC10952721 DOI: 10.1111/all.15865] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 07/06/2023] [Accepted: 07/12/2023] [Indexed: 09/14/2023]
Abstract
BACKGROUND The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen-exposed but non-sensitized subjects has not been studied in detail. OBJECTIVE To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1-specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1-induced basophil activation. METHODS Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non-allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG1 and IgG4 reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N-terminal (F1) and C-terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro-array analysis. The ability of Bet v 1-specific serum antibodies from non-allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1-derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non-allergic subjects to modulate Bet v 1-induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients. RESULTS IgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG1 and IgG4 antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen-containing food. Natural Bet v 1-specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1-specific basophil activation. CONCLUSION IgE and IgG antibodies from BPA patients and birch pollen-exposed non-sensitized subjects recognize different epitopes. These findings explain why natural allergen-specific IgG do not protect against allergic symptoms and suggest that allergen-specific IgE and IgG have different clonal origin.
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Affiliation(s)
- Georgii Brazhnikov
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
- Institute for Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Evgenii Smolnikov
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
- Department of Immunology, Institute of MedicineRUDN UniversityMoscowRussia
| | - Alla Litovkina
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
- Department of Immunology, Institute of MedicineRUDN UniversityMoscowRussia
| | - Tianchi Jiang
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Artem Shatilov
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
| | - Inna Tulaeva
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
- Laboratory of Immunopathology, Department of Clinical Immunology and AllergologyI.M. Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia
| | - Mikhail Tulaev
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Alexander Karaulov
- Laboratory of Immunopathology, Department of Clinical Immunology and AllergologyI.M. Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia
| | - Alina Poroshina
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
| | - Yury Zhernov
- F. Erismann Institute of Public HealthI.M. Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia
| | - Margarete Focke‐Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
- Karl Landsteiner University of Health SciencesKremsAustria
| | - Milena Weber
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Oluwatoyin Akinfenwa
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Olga Elisyutina
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
- Department of Immunology, Institute of MedicineRUDN UniversityMoscowRussia
| | - Sergey Andreev
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
| | - Igor Shilovskiy
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
| | - Nadezhda Shershakova
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
| | - Valeriy Smirnov
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
| | - Elena Fedenko
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
| | | | - Evgeny Cronidovich Beltyukov
- Department of Faculty Therapy, Endocrinology, Allergology and ImmunologyUral State Medical UniversityYekaterinburgRussia
| | - Veronika Victorovna Naumova
- Department of Faculty Therapy, Endocrinology, Allergology and ImmunologyUral State Medical UniversityYekaterinburgRussia
| | - Michael Kundi
- Institute for Hygiene and Applied Immunology, Center for Public HealthMedical University of ViennaViennaAustria
| | - Musa Khaitov
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
- Pirogov Russian National Research Medical UniversityMoscowRussia
| | - Ursula Wiedermann
- Institute for Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
- National Research Center Institute of Immunology Federal Medical‐Biological Agency of RussiaMoscowRussia
- Laboratory of Immunopathology, Department of Clinical Immunology and AllergologyI.M. Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia
- Karl Landsteiner University of Health SciencesKremsAustria
| | - Raffaela Campana
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
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15
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Prickler L, Baranyi U, Mengrelis K, Weijler AM, Kainz V, Kratzer B, Steiner R, Mucha J, Rudoph E, Pilat N, Bohle B, Strobl H, Pickl WF, Valenta R, Linhart B, Wekerle T. Adoptive transfer of allergen-expressing B cells prevents IgE-mediated allergy. Front Immunol 2023; 14:1286638. [PMID: 38077381 PMCID: PMC10703460 DOI: 10.3389/fimmu.2023.1286638] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 10/27/2023] [Indexed: 12/18/2023] Open
Abstract
Introduction Prophylactic strategies to prevent the development of allergies by establishing tolerance remain an unmet medical need. We previously reported that the transfer of autologous hematopoietic stem cells (HSC) expressing the major timothy grass pollen allergen, Phl p 5, on their cell surface induced allergen-specific tolerance in mice. In this study, we investigated the ability of allergen-expressing immune cells (dendritic cells, CD4+ T cells, CD8+ T cells, and CD19+ B cells) to induce allergen-specific tolerance in naive mice and identified CD19+ B cells as promising candidates for allergen-specific cell therapy. Methods For this purpose, CD19+ B cells were isolated from Phl p 5-transgenic BALB/c mice and transferred to naive BALB/c mice, pre-treated with a short course of rapamycin and an anti-CD40L antibody. Subsequently, the mice were subcutaneously sensitized three times at 4-week intervals to Phl p 5 and Bet v 1 as an unrelated control allergen. Allergen-expressing cells were followed in the blood to monitor molecular chimerism, and sera were analyzed for Phl p 5- and Bet v 1-specific IgE and IgG1 levels by RBL assay and ELISA, respectively. In vivo allergen-induced lung inflammation was measured by whole-body plethysmography, and mast cell degranulation was determined by skin testing. Results The transfer of purified Phl p 5-expressing CD19+ B cells to naive BALB/c mice induced B cell chimerism for up to three months and prevented the development of Phl p 5-specific IgE and IgG1 antibody responses for a follow-up period of 26 weeks. Since Bet v 1 but not Phl p 5-specific antibodies were detected, the induction of tolerance was specific for Phl p 5. Whole-body plethysmography revealed preserved lung function in CD19+ B cell-treated mice in contrast to sensitized mice, and there was no Phl p 5-induced mast cell degranulation in treated mice. Discussion Thus, we demonstrated that the transfer of Phl p 5-expressing CD19+ B cells induces allergen-specific tolerance in a mouse model of grass pollen allergy. This approach could be further translated into a prophylactic regimen for the prevention of IgE-mediated allergy in humans.
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Affiliation(s)
- Lisa Prickler
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Ulrike Baranyi
- Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
| | - Konstantinos Mengrelis
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Anna Marianne Weijler
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Verena Kainz
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Bernhard Kratzer
- Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Romy Steiner
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Jasmin Mucha
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Elisa Rudoph
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Nina Pilat
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Barbara Bohle
- Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Herbert Strobl
- Division of Immunology and Pathophysiology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, Graz, Austria
| | - Winfried Franz Pickl
- Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria
| | - Rudolf Valenta
- Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria
- Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, National Research Center (NRC), Moscow, Russia
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Birgit Linhart
- Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Thomas Wekerle
- Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria
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16
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Campion NJ, Villazala-Merino S, Thwaites RS, Stanek V, Killick H, Pertsinidou E, Zghaebi M, Toth J, Fröschl R, Perkmann T, Gangl K, Schneider S, Ristl R, Scott IC, Cohen ES, Molin M, Focke-Tejkl M, Regelsberger G, Hansel TT, Valenta R, Niederberger-Leppin V, Eckl-Dorna J. Nasal IL-13 production identifies patients with late-phase allergic responses. J Allergy Clin Immunol 2023; 152:1167-1178.e12. [PMID: 37536510 DOI: 10.1016/j.jaci.2023.06.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 05/09/2023] [Accepted: 06/23/2023] [Indexed: 08/05/2023]
Abstract
BACKGROUND There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regard to the "late allergic response," which occurs in approximately 40% to 50% of patients with allergy. OBJECTIVE We sought to characterize the immunologic and clinical nasal responses to birch pollen allergen challenge with a special focus on the late allergic response. METHODS In this randomized, double-blind, placebo-controlled trial, birch pollen-allergic participants were challenged with birch pollen extract (n = 20) or placebo (n = 10) on 3 consecutive days. On days 1 and 3, nasal secretions were collected at selected time points over a 24-hour time course for the measurement of 33 inflammatory mediators. Clinical responses were determined through subjective symptom scores and objective nasal airflow measurements. RESULTS Provoked participants had significantly greater clinical responses and showed significant increases in tryptase and the soluble IL-33 receptor serum stimulation 2 (sST2) in nasal secretions within minutes compared with the placebo group. Eight of 20 provoked participants displayed high IL-13 levels 2 to 8 hours after allergen provocation. This group also showed significant changes in clinical parameters, with a secondary drop in nasal airflow measured by peak nasal inspiratory flow and increased symptoms of nasal obstruction, which significantly differed from IL-13 nonresponders after 6 hours. CONCLUSIONS IL-13 response status correlates with clinical responses and type 2 cytokine responses in the late phase after allergen provocation.
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Affiliation(s)
- Nicholas J Campion
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | | | - Ryan S Thwaites
- National Heart and Lung Institute, Imperial College of London, London, United Kingdom
| | - Victoria Stanek
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Helen Killick
- Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom
| | | | - Mohammed Zghaebi
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Josef Toth
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Renate Fröschl
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Katharina Gangl
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Sven Schneider
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Robin Ristl
- Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Ian C Scott
- Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom
| | - Emma Suzanne Cohen
- Bioscience Asthma, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom
| | - Magnus Molin
- Research and Development, Thermo Fisher Scientific, Uppsala, Sweden
| | - Margit Focke-Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria; Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Guenther Regelsberger
- Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Trevor T Hansel
- National Heart and Lung Institute, Imperial College of London, London, United Kingdom
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria; Karl Landsteiner University of Health Sciences, Krems, Austria
| | | | - Julia Eckl-Dorna
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
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17
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Gülen T. A Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis. Diagnostics (Basel) 2023; 13:3307. [PMID: 37958203 PMCID: PMC10647312 DOI: 10.3390/diagnostics13213307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 11/15/2023] Open
Abstract
Our knowledge of biology and mast cell (MC) function, as well as disorders associated with the pathologic activation of MCs, has evolved over the last few decades. Anaphylaxis, mast cell activation syndrome (MCAS), and mastocytosis are interrelated yet distinct conditions within the spectrum of mast cell activation disorders. Nevertheless, all three conditions can co-exist in one and the same patient, as pathologic MC activation is the key finding in all three. When mediator release is excessive and involves multiple systems, anaphylaxis and MCAS may occur. Furthermore, mastocytosis is a clonal disorder of MCs and often presents with anaphylaxis and MCAS. Nevertheless, in some cases, even the proliferative and accumulative features of MCs in mastocytosis can account for symptoms and disease progression. In each case, diagnosis can be only made when the diagnostic consensus criteria are fulfilled. The current article aims to provide a concise clinical update and pinpoint the main difficulties in diagnosing these puzzling disorders of MCs in medical practice.
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Affiliation(s)
- Theo Gülen
- Department of Respiratory Medicine and Allergy, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, 171 77 Stockholm, Sweden
- Department of Medicine Huddinge, Karolinska Institutet, 141 52 Stockholm, Sweden
- Mastocytosis Centre Karolinska, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden
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18
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Podzhilkova A, Nagl C, Hoffmann-Sommergruber K. Molecular allergology and its application in prevention, diagnosis and therapy. FRONTIERS IN ALLERGY 2023; 4:1260902. [PMID: 37608929 PMCID: PMC10441244 DOI: 10.3389/falgy.2023.1260902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 07/28/2023] [Indexed: 08/24/2023] Open
Abstract
Allergic diseases represent a relevant global health problem, affecting adults and children and posing a significant burden for health care systems. In addition, the disease is still under-recognized and harmonized diagnostic tools and management plans for patients are still lacking. In this review the most important aspects of the diagnosis of allergic diseases are summarized and the contribution of Molecular allergology to this area is highlighted.
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Affiliation(s)
| | | | - Karin Hoffmann-Sommergruber
- Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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19
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Lu J, Hou Y, Si M, Zhu Q, Jia X, Lv Y, Wang C, He H. 5-Hydroxymethylfurfural multimers induce pseudo-allergic reaction through FcεRI at high doses. J Appl Toxicol 2023; 43:1130-1138. [PMID: 36807361 DOI: 10.1002/jat.4448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/07/2023] [Accepted: 02/15/2023] [Indexed: 02/21/2023]
Abstract
Under acidic and high temperature conditions, 5-hydroxymethylfurfural (5-HMF) converted from sugar further produces dimers (Compound II) and trimers (Compound III). The polymers were less reported, and sensitization effect of them was reported in this study. Compounds II and III induced the local and systemic anaphylaxis effect in passive cutaneous anaphylaxis mice model and activated RBL-2H3 cell inducing [Ca2+ ] mobilization, resulting in the release of β-hexosaminidase and histamine in vitro. The gene knockdown assay figured out that Compounds II and III induced degranulation through FcεRI. Further, Compounds II and III had a certain affinity with FcεRI by cell membrane chromatography and may combine on the "proline sandwich" structure indicated by molecular docking. All above suggested Compounds II and III can induce pseudo-allergic reaction through FcεRI in vivo and in vitro. Our work provides basic research to prove that the newly discovered 5-HMF transformants, Compounds II and III, induce pseudo-allergic reaction in vitro and in vivo through FcεRI, which is different pathway from 5-HMF. In foods with high sugar content, the sensitization of Compounds II and III needs more attention. In high-sugar foods and medicines, especially traditional Chinese medicine injections, the content of transformants needs to be detected.
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Affiliation(s)
- Jiayu Lu
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yajing Hou
- Department of Pharmacy, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
| | - Min Si
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Qiumei Zhu
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xin Jia
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yuexin Lv
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Cheng Wang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Huaizhen He
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China
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20
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Khan T, Ledoux IM, Aziz F, Al Ali F, Chin-Smith E, Ata M, Karim MY, Marr N. Associations between HLA class II alleles and IgE sensitization to allergens in the Qatar Biobank cohort. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. GLOBAL 2023; 2:100117. [PMID: 37779520 PMCID: PMC10509938 DOI: 10.1016/j.jacig.2023.100117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 01/16/2023] [Accepted: 02/05/2023] [Indexed: 10/03/2023]
Abstract
Background Allergic disorders are the consequence of IgE sensitization to allergens. Population studies have shown that certain human leukocyte antigen (HLA) alleles are associated with increased or decreased risk of developing allergy. Objective We aimed to characterize the relationship between HLA class II allelic diversity and IgE sensitization in an understudied Arab population. Methods We explored associations between IgE sensitization to 7 allergen mixes and mesquite (comprising 41 food or aeroallergens) and 45 common classical HLA class II alleles in a well-defined cohort of 797 individuals representing the general adult population of Qatari nationals and long-term residents. To do so, we performed HLA calling from whole genome sequencing data at 2-field resolution using 2 independent algorithms. We then applied 3 different regression models to assess either each allergen mix independently, in the context of IgE sensitization to other allergens tested, or polysensitization. Results More than half (n = 447) of the study participants showed IgE sensitization to at least 1 allergen, most of them (n = 400) to aeroallergens (Phadiatop). We identified statistically significant negative and positive associations with 24 HLA class II alleles. These have been reported to confer risk or protection from variety of diseases; however, only a few have previously been associated with allergy in other populations. Conclusions Our study reveals several new risk and protective genetic markers for allergen-specific IgE sensitization. This is a first and essential step toward a better understanding of the origins of allergic diseases in this understudied population.
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Affiliation(s)
- Taushif Khan
- Department of Human Immunology, Sidra Medicine, Doha, Qatar
- Department of Computational Science, The Jackson Laboratory, Farmington, Conn
| | | | - Ferdousey Aziz
- the Department of Pathology, Sidra Medicine, Doha, Qatar
| | - Fatima Al Ali
- Department of Human Immunology, Sidra Medicine, Doha, Qatar
| | | | - Manar Ata
- Department of Human Immunology, Sidra Medicine, Doha, Qatar
| | - Mohammed Yousuf Karim
- the Department of Pathology, Sidra Medicine, Doha, Qatar
- the College of Medicine, Qatar University, Doha, Qatar
| | - Nico Marr
- Department of Human Immunology, Sidra Medicine, Doha, Qatar
- the College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
- Institute of Translational Immunology, Brandenburg Medical School, Brandenburg an der Havel, Germany
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21
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McClements IF, McClements DJ. Designing healthier plant-based foods: Fortification, digestion, and bioavailability. Food Res Int 2023; 169:112853. [PMID: 37254427 DOI: 10.1016/j.foodres.2023.112853] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 04/12/2023] [Accepted: 04/14/2023] [Indexed: 06/01/2023]
Abstract
Many consumers are incorporating more plant-based foods into their diets as a result of concerns about the environmental, ethical, and health impacts of animal sourced foods like meat, seafood, egg, and dairy products. Foods derived from animals negatively impact the environment by increasing greenhouse gas emissions, land use, water use, pollution, deforestation, and biodiversity loss. The livestock industry confines and slaughters billions of livestock animals each year. There are concerns about the negative impacts of some animal sourced foods, such as red meat and processed meat, on human health. The livestock industry is a major user of antibiotics, which is leading to a rise in the resistance of several pathogenic microorganisms to antibiotics. It is often assumed that a plant-based diet is healthier than one containing more animal sourced foods, but this is not necessarily the case. Eating more fresh fruits, vegetables, nuts, and whole grain cereals has been linked to improved health outcomes but it is unclear whether next-generation plant-based foods, such as meat, seafood, egg, and dairy analogs are healthier than the products they are designed to replace. Many of these new products are highly processed foods that contain high levels of saturated fat, sugar, starch, and salt, and low levels of micronutrients, nutraceuticals, and dietary fibers. Moreover, they are often rapidly digested in the gastrointestinal tract because processing disrupts plant tissues and releases the macronutrients. Consequently, it is important to formulate plant-based foods to reduce the levels of nutrients linked to adverse health effects and increase the levels linked to beneficial health effects. Moreover, it is important to design the food matrix so that the macronutrients are not digested and absorbed too quickly, but the micronutrients are highly bioavailable. In this article, we discuss how next-generation plant-based foods can be made healthier by controlling their nutrient profile, digestibility, and bioavailability.
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22
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Zbîrcea LE, Buzan MR, Grijincu M, Babaev E, Stolz F, Valenta R, Păunescu V, Panaitescu C, Chen KW. Relationship between IgE Levels Specific for Ragweed Pollen Extract, Amb a 1 and Cross-Reactive Allergen Molecules. Int J Mol Sci 2023; 24:ijms24044040. [PMID: 36835455 PMCID: PMC9962666 DOI: 10.3390/ijms24044040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/05/2023] [Accepted: 02/15/2023] [Indexed: 02/19/2023] Open
Abstract
Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and calcium-binding allergens Amb a 9 and Amb a 10. To assess the importance of Amb a 1, profilin and calcium-binding allergen, the IgE reactivity profiles of clinically well-characterized 150 ragweed pollen-allergic patients were analysed regarding specific IgE levels for Amb a 1 and cross-reactive allergen molecules by quantitative ImmunoCAP measurements, IgE ELISA and by basophil activation experiments. By quantifying allergen-specific IgE levels we found that Amb a 1-specific IgE levels accounted for more than 50% of ragweed pollen-specific IgE in the majority of ragweed pollen-allergic patients. However, approximately 20% of patients were sensitized to profilin and the calcium-binding allergens, Amb a 9 and Amb a 10, respectively. As shown by IgE inhibition experiments, Amb a 8 showed extensive cross-reactivity with profilins from birch (Bet v 2), timothy grass (Phl p 12) and mugwort pollen (Art v 4) and was identified as a highly allergenic molecule by basophil activation testing. Our study indicates that molecular diagnosis performed by the quantification of specific IgE to Amb a 1, Amb a 8, Amb a 9 and Amb a 10 is useful to diagnose genuine sensitization to ragweed pollen and to identify patients who are sensitized to highly cross-reactive allergen molecules present in pollen from unrelated plants, in order to enable precision medicine-based approaches for the treatment and prevention of pollen allergy in areas with complex pollen sensitization.
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Affiliation(s)
- Lauriana-Eunice Zbîrcea
- Center of Immuno-Physiology and Biotechnologies, Department of Functional Sciences, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania
- OncoGen Center, Pius Brinzeu County Clinical Emergency Hospital, 300723 Timisoara, Romania
| | - Maria-Roxana Buzan
- Center of Immuno-Physiology and Biotechnologies, Department of Functional Sciences, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania
- OncoGen Center, Pius Brinzeu County Clinical Emergency Hospital, 300723 Timisoara, Romania
| | - Manuela Grijincu
- Center of Immuno-Physiology and Biotechnologies, Department of Functional Sciences, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania
- OncoGen Center, Pius Brinzeu County Clinical Emergency Hospital, 300723 Timisoara, Romania
| | - Elijahu Babaev
- Vienna Competence Center, Biomay AG, 1090 Vienna, Austria
| | - Frank Stolz
- Vienna Competence Center, Biomay AG, 1090 Vienna, Austria
| | - Rudolf Valenta
- Center of Pathophysiology, Infectiology and Immunology, Department of Pathophysiology and Allergy Research, Division of Immunopathology, Medical University of Vienna, 1090 Vienna, Austria
- Laboratory for Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia
- Karl Landsteiner University of Health Sciences, 3500 Krems, Austria
- NRC Institute of Immunology FMBA of Russia, 115522 Moscow, Russia
| | - Virgil Păunescu
- Center of Immuno-Physiology and Biotechnologies, Department of Functional Sciences, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania
- OncoGen Center, Pius Brinzeu County Clinical Emergency Hospital, 300723 Timisoara, Romania
| | - Carmen Panaitescu
- Center of Immuno-Physiology and Biotechnologies, Department of Functional Sciences, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania
- OncoGen Center, Pius Brinzeu County Clinical Emergency Hospital, 300723 Timisoara, Romania
- Correspondence: ; Tel.: +40-721-434-100
| | - Kuan-Wei Chen
- OncoGen Center, Pius Brinzeu County Clinical Emergency Hospital, 300723 Timisoara, Romania
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23
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Weichwald C, Zettl I, Ellinger I, Niespodziana K, Waltl EE, Villazala-Merino S, Ivanov D, Eckl-Dorna J, Niederberger-Leppin V, Valenta R, Flicker S. Antibody Conjugates Bispecific for Pollen Allergens and ICAM-1 with Potential to Prevent Epithelial Allergen Transmigration and Rhinovirus Infection. Int J Mol Sci 2023; 24:ijms24032725. [PMID: 36769047 PMCID: PMC9917280 DOI: 10.3390/ijms24032725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/13/2023] [Accepted: 01/20/2023] [Indexed: 02/04/2023] Open
Abstract
Allergy and rhinovirus (RV) infections are major triggers for rhinitis and asthma, causing a socioeconomic burden. As RVs and allergens may act synergistically to promote airway inflammation, simultaneous treatment strategies for both causative agents would be innovative. We have previously identified the transmembrane glycoprotein intercellular adhesion molecule 1 (ICAM-1) as an anchor for antibody conjugates bispecific for ICAM-1 and Phleum pratense (Phl p) 2, a major grass pollen allergen, to block allergen transmigration through the epithelial barrier. Since ICAM-1 is a receptor for the major group RVs, we speculated that our bispecific antibody conjugates may protect against RV infection. Therefore, we created antibody conjugates bispecific for ICAM-1 and the major grass pollen allergen Phl p 5 and analyzed their capacity to affect allergen penetration and RV infection. Bispecific antibody conjugates significantly reduced the trans-epithelial migration of Phl p 5 and thus the basolateral Phl p 5 concentration and allergenic activity as determined by humanized rat basophilic leukemia cells and inhibited RV infection of cultured epithelial cells. A reduction in allergenic activity was obtained only through the prevention of allergen transmigration because the Phl p 5-specific IgG antibody did not block the allergen-IgE interaction. Our results indicate the potential of allergen/ICAM-1-specific antibody conjugates as a topical treatment strategy for allergy and RV infections.
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Affiliation(s)
- Christina Weichwald
- Division of Immunopathology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Ines Zettl
- Division of Immunopathology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Isabella Ellinger
- Division of Cellular and Molecular Pathophysiology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Katarzyna Niespodziana
- Division of Immunopathology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Eva E. Waltl
- Department of Otorhinolaryngology, Medical University of Vienna, 1090 Vienna, Austria
| | | | - Daniel Ivanov
- Division of Immunopathology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
| | - Julia Eckl-Dorna
- Department of Otorhinolaryngology, Medical University of Vienna, 1090 Vienna, Austria
| | | | - Rudolf Valenta
- Division of Immunopathology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
- Karl Landsteiner University of Health Sciences, 3500 Krems, Austria
- National Research Centre (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, 115478 Moscow, Russia
- Laboratory for Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119435 Moscow, Russia
| | - Sabine Flicker
- Division of Immunopathology, Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
- Correspondence: ; Tel.: +43-1-40400-51150
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24
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Sharma K, Akre S, Chakole S, Wanjari MB. Allergic Rhinitis and Treatment Modalities: A Review of Literature. Cureus 2022; 14:e28501. [PMID: 36185919 PMCID: PMC9514154 DOI: 10.7759/cureus.28501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 08/28/2022] [Indexed: 11/10/2022] Open
Abstract
Allergic rhinitis is a highly prevalent disease affecting the quality of life of millions of patients. Immunotherapy, medication, and allergen avoidance are all part of the treatment for allergic rhinitis. Allergic rhinitis causes an increase in inflammation throughout the body. As a result, asthma, chronic hyperplastic eosinophilic sinusitis, nasal polyposis, and serous otitis media are all associated with allergic rhinitis. Treatment that is effective should target systemic inflammation and its underlying causes. It has a negative impact on work productivity and academic achievement in both children and adults. Understanding the pathophysiology of allergic rhinitis, how it relates to its comorbid disorders, and how different therapy choices affect the pathophysiology of both allergic rhinitis and its related comorbidities are essential for providing effective treatment. As the quality of air around us is changing, there is an increased chance of allergies. Along with nasal and ocular symptoms that are directly linked to the allergic process, these symptoms' interference with sleep results in daytime tiredness and a decreased quality of life. In this paper, we look at pathogenesis, causes, signs, symptoms, and treatment modalities in patients with allergic rhinitis.
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25
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Valent P, Hartmann K, Bonadonna P, Gülen T, Brockow K, Alvarez-Twose I, Hermine O, Niedoszytko M, Carter MC, Hoermann G, Butterfield JH, Lyons JJ, Sperr WR, Greiner G, Sotlar K, Kluin-Nelemans HC, Schwaab J, Lange M, George TI, Siebenhaar F, Broesby-Olsen S, Jawhar M, Nedoszytko B, Castells M, Orfao A, Gotlib J, Reiter A, Horny HP, Triggiani M, Arock M, Metcalfe DD, Akin C. Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:1941-1950. [PMID: 35623575 DOI: 10.1016/j.jaip.2022.05.007] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 05/04/2022] [Accepted: 05/11/2022] [Indexed: 12/18/2022]
Abstract
Mast cell activation (MCA) is common and occurs in a number of pathologic conditions, including IgE-dependent and independent allergic reactions, atopic disorders, autoimmune processes, and mastocytosis. In a subset of patients, no underlying disease and no known trigger of MCA are found. When the symptoms are severe, systemic, and recurrent, and accompanied by a diagnostic increase in the serum tryptase level or other mast cell mediators, an MCA syndrome (MCAS) may be diagnosed. In these patients, the symptoms typically respond to drugs suppressing MCA, mediator production in mast cells, or mediator effects. In each case, diagnostic consensus criteria must be fulfilled to diagnose MCAS. In other patients, MCA may be local, less severe, or less acute, or may be suspected but not confirmed, so that the diagnostic criteria of MCAS are not fulfilled. In these patients, it may be difficult to prove MCA, for example, by measuring multiple mast cell mediators or basophil activation, the latter as a surrogate of IgE-dependent hypersensitivity. However, validated diagnostic criteria for implicating suspected MCA behind such conditions are lacking, even if some of these conditions have recently been assigned to an International Classification of Diseases-10-Clinical Modification code (ICD-10-CM). In this article, we discuss diagnostic features and criteria and propose a ICD-10-CM-adjusted classification for disorders associated with MCA, herein referred to as MCA disorders (MCADs), with special emphasis on the delineation between confirmed MCAS, MCAD not fulfilling MCAS criteria, and suspected MCAD that is not present. In addition, we discuss the discrimination between overt MCAD and predisposing conditions, such as atopic states, mastocytosis, and hereditary alpha tryptasemia.
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Affiliation(s)
- Peter Valent
- Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
| | - Karin Hartmann
- Division of Allergy, Department of Dermatology, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland
| | | | - Theo Gülen
- Department of Respiratory Medicine and Allergy, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden
| | - Knut Brockow
- Department of Dermatology and Allergy Biederstein, Technical University of Munich, Munich, Germany
| | - Ivan Alvarez-Twose
- Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast) and CIBERONC, Hospital Virgen del Valle, Toledo, Spain
| | - Olivier Hermine
- Service d'hématologie, Imagine Institute Université de Paris, Sorbonne, INSERM U1163, Centre national de référence des mastocytoses, Hôpital Necker, Assistance publiquehôpitaux de Paris, Paris, France
| | - Marek Niedoszytko
- Department of Allergology, Medical University of Gdansk, Gdansk, Poland
| | - Melody C Carter
- Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Gregor Hoermann
- Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria; MLL Munich Leukemia Laboratory, Munich, Germany
| | | | - Jonathan J Lyons
- Translational Allergic Immunopathology Unit, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Wolfgang R Sperr
- Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria
| | - Georg Greiner
- Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, and Ihr Labor, Vienna, Austria
| | - Karl Sotlar
- Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Hanneke C Kluin-Nelemans
- Department of Haematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Juliana Schwaab
- Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany
| | - Magdalena Lange
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland
| | - Tracy I George
- Department of Pathology, University of Utah, Salt Lake City, Utah
| | - Frank Siebenhaar
- Institute of Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany
| | - Sigurd Broesby-Olsen
- Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark
| | - Mohamad Jawhar
- Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany
| | - Boguslaw Nedoszytko
- Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland; Invicta Fertility and Reproductive Center, Molecular Laboratory, Sopot, Poland
| | - Mariana Castells
- Division of Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
| | - Alberto Orfao
- Servicio Central de Citometria, Centro de Investigacion del Cancer (IBMCC; CSIC/USAL), Instituto Biosanitario de Salamanca (IBSAL), CIBERONC and Department of Medicine, University of Salamanca, Salamanca, Spain
| | - Jason Gotlib
- Stanford Cancer Institute/Stanford University School of Medicine, Stanford, Calif
| | - Andreas Reiter
- Department of Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany
| | - Hans-Peter Horny
- Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany
| | - Massimo Triggiani
- Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy
| | - Michel Arock
- Department of Hematological Biology, Pitié-Salpêtrière Hospital, Pierre et Marie Curie University (UPMC), Paris, France
| | - Dean D Metcalfe
- Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
| | - Cem Akin
- Division of Allergy and Clinical Immunology, University of Michigan, Ann Arbor, Mich
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Mittermann I, Lupinek C, Wieser S, Aumayr M, Kuchler WW, Chan AW, Lee TH, Zieglmayer P. IgE reactivity patterns in Asian and central European cockroach-sensitized patients reveal differences in primary sensitizing allergen sources. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. GLOBAL 2022; 1:145-153. [PMID: 37781268 PMCID: PMC10509942 DOI: 10.1016/j.jacig.2022.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/17/2022] [Accepted: 04/08/2022] [Indexed: 10/03/2023]
Abstract
Background The prevalence of cockroach (CR) sensitization and its relevance as a trigger of allergy symptoms differs greatly in different geographic areas. Objective This study aimed to compare molecular IgE reactivity profiles in CR-sensitized patients with perennial allergy symptoms from Hong Kong (HK) and Austria and identify the main primary sensitizers. Methods IgE sensitization was assessed by skin prick test and/or IgE reactivity with CR extract. Molecular IgE reactivity profiles were analyzed via multiplex assay for sensitization to allergens and extracts from CR, house dust mite (HDM), shellfish, and 3 additional insect species. Results HDM was the main primary sensitizer in both cohorts. In the HK group, genuine sensitization to CR was found in 45%, but none of the patients in the Austrian cohort was truly sensitized to that allergen source. Most patients from HK were cross-sensitized to other insects and/or shellfish, presumably by broad reactivity to tropomyosin and arginine kinase. About half of Austrian subjects lacked IgE to these pan-allergens, indicating co- but not cross-sensitization to insects and/or shellfish. Regarding IgE recognition frequencies, arginine kinases (64% HK, 10% Austria) and tropomyosins (42% HK, 15% Austria) were most frequently recognized; Bla g 4 (lipocalin) was detected in HK patients only (42%). Tropomyosin (Per a 7) was significantly more frequently recognized in patients with asthma. Sera from HDM-sensitized subjects from HK showed a higher proportion of sensitization to minor mite allergens. Conclusion Molecular profiling identified differences between CR-sensitized allergic patients from HK and Austria in terms of primary sensitizers and molecular IgE reactivity patterns. Tropomyosin from American cockroach (Per a 7) was shown to be significantly associated with asthma symptoms and might be suitable as biomarker for more severe respiratory allergy symptoms.
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Affiliation(s)
| | | | | | | | | | - Alson W.M. Chan
- Allergy Centre, Hong Kong Sanatorium and Hospital, Hong Kong, China
| | - Tak Hong Lee
- Allergy Centre, Hong Kong Sanatorium and Hospital, Hong Kong, China
| | - Petra Zieglmayer
- Vienna Challenge Chamber, Vienna, Austria
- Karl Landsteiner University, Krems, Austria
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Hu Y, Wang Y, Lin J, Wu S, Muyldermans S, Wang S. Versatile Application of Nanobodies for Food Allergen Detection and Allergy Immunotherapy. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:8901-8912. [PMID: 35820160 DOI: 10.1021/acs.jafc.2c03324] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The unique characteristics of camelid heavy-chain only antibody (HCAb) derived nanobodies (Nbs) have facilitated their employment as tools for research and application in extensive fields including food safety inspection, diagnosis and therapy of diseases, etc., to develop immune detecting techniques or alternative candidates of conventional antibodies as diagnostic and therapeutic reagents. The wide application in the fields of food allergen inspection and immunotherapy has not been addressed as not much results published in the literature. The robust properties and straightforward selecting strategy of Nbs impel the advantageous employment compared with monoclonal antibodies (mAbs) to establish immunoassay and serve as blocking antibodies to compete immunoglobulin E (IgE) binding epitopes on food allergens. More and more efforts have been invested to develop specific Nbs against food allergen proteins, such as macadamia allergen of Mac i 1, peanut allergen of Ara h 3, and lupine allergen of Lup an 1, which demonstrated the potential of Nbs for research and application in food allergen surveillance. Meanwhile, the paratopes of Nbs preferably targeting the unique epitopes of food allergens can provide more possibilities to serve as blocking antibodies to shield IgE binding epitopes for food allergy immunotherapy. Regardless, the research and application of Nbs in the field of food allergen and allergic reactions are expected to attract dramatic focus and produce promising research outputs.
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Affiliation(s)
- Yaozhong Hu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Yi Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Jing Lin
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Sihao Wu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Serge Muyldermans
- Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium
| | - Shuo Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
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Wang C, Hu T, Lu J, Lv Y, Ge S, Hou Y, He H. Convenient Diaryl Ureas as Promising Anti-pseudo-allergic Agents. J Med Chem 2022; 65:10626-10637. [PMID: 35876064 DOI: 10.1021/acs.jmedchem.2c00846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Cheng Wang
- School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76, Yanta West Road, Xi’an, Shaanxi 710061, China
| | - Tian Hu
- Department of Pharmacy, 3201 Hospital Affiliated to Xi’an Jiaotong University, Hanzhong, Shaanxi 723000, China
| | - Jiayu Lu
- School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76, Yanta West Road, Xi’an, Shaanxi 710061, China
| | - Yuexin Lv
- School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76, Yanta West Road, Xi’an, Shaanxi 710061, China
| | - Shuai Ge
- School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76, Yanta West Road, Xi’an, Shaanxi 710061, China
| | - Yajing Hou
- Department of Pharmacy, Shaanxi Province People’s Hospital, Xi’an, Shaanxi 710068, China
| | - Huaizhen He
- School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76, Yanta West Road, Xi’an, Shaanxi 710061, China
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Garib V, Ben‐Ali M, Kundi M, Curin M, Yaakoubi R, Ben‐Mustapha I, Mekki N, Froeschl R, Perkmann T, Valenta R, Barbouche M. Profound differences in IgE and IgG recognition of micro-arrayed allergens in hyper-IgE syndromes. Allergy 2022; 77:1761-1771. [PMID: 34653276 PMCID: PMC9298271 DOI: 10.1111/all.15143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 03/02/2021] [Accepted: 10/10/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND The specificities of IgE and IgG for allergen molecules in patients with inborn errors of immunity (IEI) have not been investigated in detail. OBJECTIVE To study IgE and IgG antibody specificities in patients with defined hyper-IgE syndromes (HIES) using a comprehensive panel of allergen molecules. METHODS We used chips containing micro-arrayed allergen molecules to analyze allergen-specific IgE and IgG levels in sera from two groups of HIES patients: Autosomal recessive mutations in phosphoglucomutase-3 (PGM3); Autosomal dominant negative mutations of STAT3 (STAT3); and age-matched subjects with allergic sensitizations. Assays with rat basophil leukemia cells transfected with human FcεRI were performed to study the biological relevance of IgE sensitizations. RESULTS Median total IgE levels were significantly lower in the sensitized control group (212.9 kU/L) as compared to PGM3 (5042 kU/L) and STAT3 patients (2561 kU/L). However, PGM3 patients had significantly higher allergen-specific IgE levels and were sensitized to a larger number of allergen molecules as compared to STAT3 patients. Biological relevance of IgE sensitization was confirmed for PGM3 patients by basophil activation testing. PGM3 patients showed significantly lower cumulative allergen-specific IgG responses in particular to milk and egg allergens as compared to STAT3 patients and sensitized controls whereas total IgG levels were comparable to STAT3 patients and significantly higher than in controls. CONCLUSION The analysis with multiple micro-arrayed allergen molecules reveals profound differences of allergen-specific IgE and IgG recognition in PGM3 and STAT3 patients which may be useful for classification of IEI and clinical characterization of patients.
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Affiliation(s)
- Victoria Garib
- Division of Immunopathology Department of Pathophysiology and Allergy Research Center of Pathophysiology, Infectiology and Immunology Medical University of Vienna Wien Austria
- Ministry of Innovation Development Tashkent Uzbekistan
| | - Meriem Ben‐Ali
- Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02) Department of Immunology Institut Pasteur de Tunis and University Tunis El Manar Tunis Tunisia
| | - Michael Kundi
- Department for Environmental Health Center for Public Health Medical University Vienna Wien Austria
| | - Mirela Curin
- Division of Immunopathology Department of Pathophysiology and Allergy Research Center of Pathophysiology, Infectiology and Immunology Medical University of Vienna Wien Austria
| | - Roukaya Yaakoubi
- Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02) Department of Immunology Institut Pasteur de Tunis and University Tunis El Manar Tunis Tunisia
| | - Imen Ben‐Mustapha
- Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02) Department of Immunology Institut Pasteur de Tunis and University Tunis El Manar Tunis Tunisia
| | - Najla Mekki
- Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02) Department of Immunology Institut Pasteur de Tunis and University Tunis El Manar Tunis Tunisia
| | - Renate Froeschl
- Department of Laboratory Medicine Medical University of Vienna Vienna Austria
| | - Thomas Perkmann
- Department of Laboratory Medicine Medical University of Vienna Vienna Austria
| | - Rudolf Valenta
- Division of Immunopathology Department of Pathophysiology and Allergy Research Center of Pathophysiology, Infectiology and Immunology Medical University of Vienna Wien Austria
- NRC Institute of Immunology FMBA of Russia Moscow Russia
- Laboratory of Immunopathology Department of Clinical Immunology and Allergology Sechenov First Moscow State Medical University Moscow Russia
- Karl Landsteiner University of Health Sciences Krems Austria
| | - Mohamed‐Ridha Barbouche
- Laboratory of Transmission, Control and Immunobiology of Infections (LR11IPT02) Department of Immunology Institut Pasteur de Tunis and University Tunis El Manar Tunis Tunisia
- Medical School University of Tunis El Manar Tunis Tunisia
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Zettl I, Ivanova T, Strobl MR, Weichwald C, Goryainova O, Khan E, Rutovskaya MV, Focke‐Tejkl M, Drescher A, Bohle B, Flicker S, Tillib SV. Isolation of nanobodies with potential to reduce patients' IgE binding to Bet v 1. Allergy 2022; 77:1751-1760. [PMID: 34837242 DOI: 10.1111/all.15191] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 11/03/2021] [Accepted: 11/18/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Recent studies showed that a single injection of human monoclonal allergen-specific IgG antibodies significantly reduced allergic symptoms in birch pollen-allergic patients. Since the production of full monoclonal antibodies in sufficient amounts is laborious and expensive, we sought to investigate if smaller recombinant allergen-specific antibody fragments, that is, nanobodies, have similar protective potential. For this purpose, nanobodies specific for Bet v 1, the major birch pollen allergen, were generated to evaluate their efficacy to inhibit IgE-mediated responses. METHODS A cDNA-VHH library was constructed from a camel immunized with Bet v 1 and screened for Bet v 1 binders encoding sequences by phage display. Selected nanobodies were expressed, purified, and analyzed in regards of epitope-specificity and affinity to Bet v 1. Furthermore, cross-reactivity to Bet v 1-homologues from alder, hazel and apple, and their usefulness to inhibit IgE binding and allergen-induced basophil activation were investigated. RESULTS We isolated three nanobodies that recognize Bet v 1 with high affinity and cross-react with Aln g 1 (alder) and Cor a 1 (hazel). Their epitopes were mapped to the alpha-helix at the C-terminus of Bet v 1. All nanobodies inhibited allergic patients' polyclonal IgE binding to Bet v 1, Aln g 1, and Cor a 1 and partially suppressed Bet v 1-induced basophil activation. CONCLUSION We identified high-affinity Bet v 1-specific nanobodies that recognize an important IgE epitope and reduce allergen-induced basophil activation revealing the first proof that allergen-specific nanobodies are useful tools for future treatment of pollen allergy.
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Affiliation(s)
- Ines Zettl
- Division of Immunopathology Institute of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | - Tatiana Ivanova
- Institute of Gene Biology Russian Academy of Sciences Moscow Russia
| | - Maria R. Strobl
- Division of Experimental Allergology Institute of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | - Christina Weichwald
- Division of Immunopathology Institute of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | | | - Evgenia Khan
- Institute of Gene Biology Russian Academy of Sciences Moscow Russia
| | - Marina V. Rutovskaya
- Institute of Gene Biology Russian Academy of Sciences Moscow Russia
- A.N.Severtsov Institute of Ecology and Evolution Russian Academy of Sciences Moscow Russia
| | - Margarete Focke‐Tejkl
- Division of Immunopathology Institute of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | | | - Barbara Bohle
- Division of Experimental Allergology Institute of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | - Sabine Flicker
- Division of Immunopathology Institute of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | - Sergei V. Tillib
- Institute of Gene Biology Russian Academy of Sciences Moscow Russia
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Nur Husna SM, Tan HTT, Md Shukri N, Mohd Ashari NS, Wong KK. Allergic Rhinitis: A Clinical and Pathophysiological Overview. Front Med (Lausanne) 2022; 9:874114. [PMID: 35463011 PMCID: PMC9021509 DOI: 10.3389/fmed.2022.874114] [Citation(s) in RCA: 92] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 03/15/2022] [Indexed: 01/25/2023] Open
Abstract
Allergic rhinitis (AR) represents a global health concern where it affects approximately 400 million people worldwide. The prevalence of AR has increased over the years along with increased urbanization and environmental pollutants thought to be some of the leading causes of the disease. Understanding the pathophysiology of AR is crucial in the development of novel therapies to treat this incurable disease that often comorbids with other airway diseases. Hence in this mini review, we summarize the well-established yet vital aspects of AR. These include the epidemiology, clinical and laboratory diagnostic criteria, AR in pediatrics, pathophysiology of AR, Th2 responses in the disease, as well as pharmacological and immunomodulating therapies for AR patients.
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Affiliation(s)
- Siti Muhamad Nur Husna
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Hern-Tze Tina Tan
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Norasnieda Md Shukri
- Department of Otorhinolaryngology, Head and Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
- Hospital Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Noor Suryani Mohd Ashari
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
| | - Kah Keng Wong
- Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia
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Farag AK, Roesner LM, Wieschowski S, Heratizadeh A, Eiz‐Vesper B, Kwok WW, Valenta R, Werfel T. Specific T cells targeting Staphylococcus aureus fibronectin-binding protein 1 induce a type 2/type 1 inflammatory response in sensitized atopic dermatitis patients. Allergy 2022; 77:1245-1253. [PMID: 34601735 PMCID: PMC11497299 DOI: 10.1111/all.15120] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 08/13/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND Atopic dermatitis (AD) is one of the most common inflammatory skin diseases worldwide and Staphylococcus aureus colonization and secondary infections occur in the majority of AD patients. Allergic sensitizations against microbial antigens have been discussed as possible trigger factors of AD. Recently, we reported IgE sensitization against fibronectin-binding protein 1 (FBP1), an essential virulence component in S. aureus, in a subgroup of patients suffering from AD. To expand these findings by investigating delayed-type immune reactions, the objective of this study was to detect and phenotypically characterize FBP1-specific T cells as possible trigger factors in AD. METHODS Immunodominant T-cell epitopes were mapped by proliferation testing of patient-derived FBP1-specific T-cell lines after stimulation with single 15mer peptides, which were derived from different functional domains of the FBP1 sequence. Major histocompatibility complex class II tetramers carrying immunodominant epitopes successfully stained T helper cells in 8 out of 8 HLA-matched, IgE-sensitized AD patients. RESULTS Cytokine profiling of multimer-sorted cells revealed that predominantly the type 2 cytokines IL-13 and IL-4 were secreted by these cells. In contrast, IL-17, the marker cytokine for response to extracellular pathogens, was scarcely detectable. CONCLUSIONS We demonstrate that FBP1 contains immunodominant peptides that induce a specific pro-inflammatory T helper cell response with increased Th2 levels that can drive an allergic inflammation in sensitized AD patients.
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Affiliation(s)
- Ahmed K. Farag
- Division of Dermatology and AllergyDepartment of Immunodermatology and Allergy ResearchHannover Medical SchoolHannoverGermany
| | - Lennart M. Roesner
- Division of Dermatology and AllergyDepartment of Immunodermatology and Allergy ResearchHannover Medical SchoolHannoverGermany
- Cluster of Excellence RESIST (EXC 2155)Hannover Medical SchoolHannoverGermany
| | - Susanne Wieschowski
- Division of Dermatology and AllergyDepartment of Immunodermatology and Allergy ResearchHannover Medical SchoolHannoverGermany
| | - Annice Heratizadeh
- Division of Dermatology and AllergyDepartment of Immunodermatology and Allergy ResearchHannover Medical SchoolHannoverGermany
| | - Britta Eiz‐Vesper
- Institute of Transfusion Medicine and Transplant EngineeringHannover Medical SchoolHannoverGermany
| | - William W. Kwok
- Benaroya Research Institute at Virginia MasonSeattleWashingtonUSA
- Department of MedicineUniversity of WashingtonSeattleWashingtonUSA
| | - Rudolf Valenta
- Division of ImmunopathologyDepartment of Pathophysiology and Allergy ResearchCenter for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
- NRC Institute of Immunology FMBA of RussiaMoscowRussia
- Department of Clinical Immunology and AllergySechenov First Moscow State Medical UniversityMoscowRussia
- Karl Landsteiner University of Health SciencesKremsAustria
| | - Thomas Werfel
- Division of Dermatology and AllergyDepartment of Immunodermatology and Allergy ResearchHannover Medical SchoolHannoverGermany
- Cluster of Excellence RESIST (EXC 2155)Hannover Medical SchoolHannoverGermany
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Synthesis and evaluation of new potential anti-pseudo-allergic agents. Bioorg Med Chem Lett 2022; 59:128575. [DOI: 10.1016/j.bmcl.2022.128575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 01/05/2022] [Accepted: 01/15/2022] [Indexed: 11/17/2022]
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Zghaebi M, Byazrova M, Flicker S, Villazala-Merino S, Campion NJ, Stanek V, Tu A, Breiteneder H, Filatov A, Khaitov M, Niederberger-Leppin V, Eckl-Dorna J, Valenta R. Tracing Human IgE B Cell Antigen Receptor-Bearing Cells With a Monoclonal Anti-Human IgE Antibody That Specifically Recognizes Non-Receptor-Bound IgE. Front Immunol 2021; 12:803236. [PMID: 34987522 PMCID: PMC8721004 DOI: 10.3389/fimmu.2021.803236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 11/08/2021] [Indexed: 11/13/2022] Open
Abstract
Up to 30% of the population suffers from immunoglobulin E (IgE)-mediated allergies. Despite current stepwise gating approaches, the unambiguous identification of human IgE-producing cells by flow cytometry and immunohistology remains challenging. This is mainly due to the scarcity of these cells and the fact that IgE is not only expressed in a membrane-bound form on the surface of IgE-producing cells in form of the B cell antigen receptor (BCR), but is more frequently found on various cell types bound to the low and high affinity receptors, CD23 and FcϵRI, respectively. Here we sought to develop a sequential gating strategy for unambiguous detection of cells bearing the IgE BCR on their surface. To that aim we first tested the monoclonal anti-IgE antibody omalizumab for its ability to discriminate between IgE BCR and receptor-bound IgE using cells producing IgE or bearing IgE bound to CD23 as well as basophils exhibiting FcϵRI receptor-bound IgE. Using flow cytometry, we demonstrated that omalizumab recognized IgE producing cells with a high sensitivity of up to 1 IgE+ cell in 1000 human peripheral blood mononuclear cells (PBMCs). These results were confirmed by confocal microscopy both in cell suspensions as well as in nasal polyp tissue sections. Finally, we established a consecutive gating strategy allowing the clear identification of class-switched, allergen-specific IgE+ memory B cells and plasmablasts/plasma cells in human PBMCs. Birch pollen specific IgE+ memory B cells represented on average 0.734% of total CD19+ B cells in allergic patients after allergen exposure. Thus, we developed a new protocol for exclusive staining of non-receptor bound allergen-specific IgE+ B cell subsets in human samples.
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MESH Headings
- Allergens/immunology
- Anti-Allergic Agents/therapeutic use
- Antibodies, Monoclonal/metabolism
- Antigens, CD19/metabolism
- Antigens, Plant/immunology
- B-Lymphocyte Subsets/immunology
- Betula/immunology
- Cell Separation
- Epitopes
- Flow Cytometry
- Humans
- Immunoglobulin Class Switching
- Immunoglobulin E/metabolism
- Immunologic Memory
- Omalizumab/therapeutic use
- Pollen/immunology
- Protein Binding
- Receptors, Antigen, B-Cell/metabolism
- Receptors, IgE/metabolism
- Rhinitis, Allergic, Seasonal/drug therapy
- Rhinitis, Allergic, Seasonal/immunology
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Affiliation(s)
- Mohammed Zghaebi
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Maria Byazrova
- National Research Centre (NRC) Institute of Immunology, Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
| | - Sabine Flicker
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | | | - Nicholas J. Campion
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Victoria Stanek
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Aldine Tu
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Heimo Breiteneder
- Division of Medical Biotechnology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Alexander Filatov
- National Research Centre (NRC) Institute of Immunology, Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia
| | - Musa Khaitov
- National Research Centre (NRC) Institute of Immunology, Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Immunology Department, Pirogov Russian National Research Medical University, Moscow, Russia
| | | | - Julia Eckl-Dorna
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
- *Correspondence: Julia Eckl-Dorna,
| | - Rudolf Valenta
- National Research Centre (NRC) Institute of Immunology, Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russia
- Karl Landsteiner University of Health Sciences, Krems, Austria
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Shamji MH, Valenta R, Jardetzky T, Verhasselt V, Durham SR, Würtzen PA, van Neerven RJ. The role of allergen-specific IgE, IgG and IgA in allergic disease. Allergy 2021; 76:3627-3641. [PMID: 33999439 PMCID: PMC8601105 DOI: 10.1111/all.14908] [Citation(s) in RCA: 155] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/03/2021] [Accepted: 05/10/2021] [Indexed: 12/28/2022]
Abstract
Immunoglobulin E (IgE)‐mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. Exposure to even minute quantities of allergens can lead to the production of IgE antibodies in atopic individuals. This is termed allergic sensitization, which occurs mainly in early childhood. Allergen‐specific IgE then binds to the high (FcεRI) and low‐affinity receptors (FcεRII, also called CD23) for IgE on effector cells and antigen‐presenting cells. Subsequent and repeated allergen exposure increases allergen‐specific IgE levels and, by receptor cross‐linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE‐facilitated allergen presentation perpetuates T cell–mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE, even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen‐specific IgG and IgA antibodies usually recognize different epitopes on allergens compared with IgE and do not efficiently interfere with allergen‐induced inflammation. However, IgG and IgA antibodies to these important IgE epitopes can be induced by allergen‐specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti‐IgE treatment does the same by preventing IgE from binding to its receptor on mast cells and basophils. Here, we review the complex interplay of allergen‐specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.
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Affiliation(s)
| | - Rudolf Valenta
- Department of Pathophysiology and Allergy Research Medical University of Vienna Vienna Austria
- Laboratory of Immunopathology Department of Clinical Immunology and Allergology Sechenov First Moscow State Medical University Moscow Russia
- NRC Institute of Immunology FMBA of Russia Moscow Russia
- Karl Landsteiner University of Health Sciences Krems Austria
| | | | - Valerie Verhasselt
- School of Molecular Sciences University of Western Australia Perth WA Australia
| | | | | | - R.J. Joost van Neerven
- Wageningen University & Research Wageningen The Netherlands
- FrieslandCampina Amersfoort The Netherlands
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Akinfenwa O, Huang HJ, Linhart B, Focke-Tejkl M, Vrtala S, Poroshina A, Nikonova A, Khaitov M, Campion NJ, Eckl-Dorna J, Niederberger-Leppin V, Kratzer B, Tauber PA, Pickl WF, Kundi M, Campana R, Valenta R. Preventive Administration of Non-Allergenic Bet v 1 Peptides Reduces Allergic Sensitization to Major Birch Pollen Allergen, Bet v 1. Front Immunol 2021; 12:744544. [PMID: 34795666 PMCID: PMC8594376 DOI: 10.3389/fimmu.2021.744544] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 09/20/2021] [Indexed: 11/15/2022] Open
Abstract
IgE-mediated allergy to birch pollen affects more than 100 million patients world-wide. Bet v 1, a 17 kDa protein is the major allergen in birch pollen responsible for allergic rhinoconjunctivitis and asthma in birch pollen allergic patients. Allergen-specific immunotherapy (AIT) based on therapeutic administration of Bet v 1-containing vaccines is an effective treatment for birch pollen allergy but no allergen-specific forms of prevention are available. We developed a mouse model for IgE sensitization to Bet v 1 based on subcutaneous injection of aluminum-hydroxide adsorbed recombinant Bet v 1 and performed a detailed characterization of the specificities of the IgE, IgG and CD4+ T cell responses in sensitized mice using seven synthetic peptides of 31-42 amino acids length which comprised the Bet v 1 sequence and the epitopes recognized by human CD4+ T cells. We then demonstrate that preventive systemic administration of a mix of synthetic non-allergenic Bet v 1 peptides to 3-4 week old mice significantly reduced allergic immune responses, including IgE, IgG, IgE-mediated basophil activation, CD4+ T cell and IL-4 responses to the complete Bet v 1 allergen but not to the unrelated major grass pollen allergen Phl p 5, without inducing Bet v 1-specific allergic sensitization or adaptive immunity. Our results thus demonstrate that early preventive administration of non-allergenic synthetic T cell epitope-containing allergen peptides could be a safe strategy for the prevention of allergen-specific IgE sensitization.
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Affiliation(s)
- Oluwatoyin Akinfenwa
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Huey-Jy Huang
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Birgit Linhart
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Margarete Focke-Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Susanne Vrtala
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Alina Poroshina
- National Research Center (NRC) - Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Alexandra Nikonova
- National Research Center (NRC) - Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Musa Khaitov
- National Research Center (NRC) - Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.,Immunology Department, Pirogov Russian National Research Medical University, Moscow, Russia
| | - Nicholas J Campion
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | - Julia Eckl-Dorna
- Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
| | | | - Bernhard Kratzer
- Institute of Immunology, Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna, Vienna, Austria
| | - Peter Anton Tauber
- Institute of Immunology, Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna, Vienna, Austria
| | - Winfried F Pickl
- Karl Landsteiner University of Health Sciences, Krems, Austria.,Institute of Immunology, Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna, Vienna, Austria
| | - Michael Kundi
- Institute for Hygiene and Applied Immunology, Centre for Public Health, Medical University of Vienna, Vienna, Austria
| | - Raffaela Campana
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,Karl Landsteiner University of Health Sciences, Krems, Austria.,National Research Center (NRC) - Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.,Laboratory for Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russia
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Liang J, Zhuang R, Sun X, Zhang F, Zou B. Apremilast mitigates interleukin (IL)-13-induced inflammatory response and mucin production in human nasal epithelial cells (hNECs). Bioengineered 2021; 12:8583-8593. [PMID: 34607526 PMCID: PMC8806939 DOI: 10.1080/21655979.2021.1987818] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Interleukin (IL)-13-associated inflammatory response is important for the pathogenesis of allergic rhinitis (AR). Apremilast is a phosphodiesterase-4 (PDE4) inhibitor approved for psoriasis treatment. Here, we investigated the potential effects of Apremilast against IL-13-induced injury in human nasal epithelial cells (hNECs). Firstly, Apremilast ameliorated oxidative stress in IL-13-challenged cells by decreasing the levels of reactive oxygen species (ROS) and the production of malondialdehyde (MDA). Secondly, Apremilast inhibited the expressions of IL-6 and IL-8. Moreover, Apremilast inhibited the expressions of the chemokines colony-stimulating factor 2 (CSF2) and chemokine ligand 11 (CCL11). Interestingly, exposure to IL-13 increased the expressions of mucin 4 and mucin 5AC (MUC5AC), which was ameliorated by treatment with Apremilast. Interestingly, we found that Apremilast inhibited the phosphorylation of c-Jun-N-terminal kinase (JNK). Importantly, Apremilast reduced the levels of c-fos and c-Jun, the two AP-1 subfamilies. The luciferase reporter assay demonstrates that Apremilast reduced the transcriptional activity of activator protein 1 (AP-1). Lastly, we found that Apremilast prevented the activation of nuclear factor kappa-B (NF-κB) by decreasing the levels of nuclear NF-κB p65 and the luciferase activity of the NF-κB reporter. In summary, we conclude that Apremilast possesses a protective effect against IL-13-induced inflammatory response and mucin production in hNECs by inhibiting the activity of AP-1 and NF-κB.
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Affiliation(s)
- Jia Liang
- Department of Otorhinolaryngology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,National Clinical Research Center for Child Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China
| | - RuoXiao Zhuang
- Department of Otorhinolaryngology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,National Clinical Research Center for Child Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China
| | - XueYao Sun
- Department of Otorhinolaryngology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,National Clinical Research Center for Child Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China
| | - Feng Zhang
- Department of Otorhinolaryngology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,National Clinical Research Center for Child Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China
| | - Bin Zou
- Department of Otorhinolaryngology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,National Clinical Research Center for Child Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.,Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China
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Üzülmez Ö, Kalic T, Mayr V, Lengger N, Tscheppe A, Radauer C, Hafner C, Hemmer W, Breiteneder H. The Major Peanut Allergen Ara h 2 Produced in Nicotiana benthamiana Contains Hydroxyprolines and Is a Viable Alternative to the E. Coli Product in Allergy Diagnosis. FRONTIERS IN PLANT SCIENCE 2021; 12:723363. [PMID: 34671372 PMCID: PMC8522509 DOI: 10.3389/fpls.2021.723363] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/17/2021] [Indexed: 05/12/2023]
Abstract
Peanut allergy is a potentially life-threatening disease that is mediated by allergen-specific immunoglobulin E (IgE) antibodies. The major peanut allergen Ara h 2, a 2S albumin seed storage protein, is one of the most dangerous and potent plant allergens. Ara h 2 is posttranslationally modified to harbor four disulfide bridges and three hydroxyprolines. These hydroxyproline residues are required for optimal IgE-binding to the DPYSPOHS motifs representing an immunodominant IgE epitope. So far, recombinant Ara h 2 has been produced in Escherichia coli, Lactococcus lactis, Trichoplusia ni insect cell, and Chlamydomonas reinhardtii chloroplast expression systems, which were all incapable of proline hydroxylation. However, molecular diagnosis of peanut allergy is performed using either natural or E. coli-produced major peanut allergens. As IgE from the majority of patients is directed to Ara h 2, it is of great importance that the recombinant Ara h 2 harbors all of its eukaryotic posttranslational modifications. We produced hydroxyproline-containing and correctly folded Ara h 2 in the endoplasmic reticulum of leaf cells of Nicotiana benthamiana plants, using the plant virus-based magnICON® transient expression system with a yield of 200 mg/kg fresh biomass. To compare prokaryotic with eukaryotic expression methods, Ara h 2 was expressed in E. coli together with the disulfide-bond isomerase DsbC and thus harbored disulfide bridges but no hydroxyprolines. The recombinant allergens from N. benthamiana and E. coli were characterized and compared to the natural Ara h 2 isolated from roasted peanuts. Natural Ara h 2 outperformed both recombinant proteins in IgE-binding and activation of basophils via IgE cross-linking, the latter indicating the potency of the allergen. Interestingly, significantly more efficient IgE cross-linking by the N. benthamiana-produced allergen was observed in comparison to the one induced by the E. coli product. Ara h 2 from N. benthamiana plants displayed a higher similarity to the natural allergen in terms of basophil activation due to the presence of hydroxyproline residues, supporting so far published data on their contribution to the immunodominant IgE epitope. Our study advocates the use of N. benthamiana plants instead of prokaryotic expression hosts for the production of the major peanut allergen Ara h 2.
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Affiliation(s)
- Öykü Üzülmez
- Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Tanja Kalic
- Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
- Department of Dermatology, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria
| | - Vanessa Mayr
- Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Nina Lengger
- Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Angelika Tscheppe
- Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Christian Radauer
- Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Christine Hafner
- Department of Dermatology, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria
- Karl Landsteiner Institute for Dermatological Research, St. Pölten, Austria
| | | | - Heimo Breiteneder
- Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
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Fuhrmann V, Huang HJ, Akarsu A, Shilovskiy I, Elisyutina O, Khaitov M, van Hage M, Linhart B, Focke-Tejkl M, Valenta R, Sekerel BE. From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack. Front Immunol 2021; 12:742732. [PMID: 34630424 PMCID: PMC8496898 DOI: 10.3389/fimmu.2021.742732] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/23/2021] [Indexed: 12/02/2022] Open
Abstract
Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.
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Affiliation(s)
- Verena Fuhrmann
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Huey-Jy Huang
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Aysegul Akarsu
- Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Igor Shilovskiy
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Olga Elisyutina
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
| | - Musa Khaitov
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University, Hospital, Stockholm, Sweden
| | - Birgit Linhart
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Margarete Focke-Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Laboratory for Molecular Allergology, National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia
- Karl Landsteiner University of Health Sciences, Krems, Austria
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Bulent Enis Sekerel
- Division of Allergy and Asthma, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
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D'souza N, Weber M, Sarzsinszky E, Vrtala S, Curin M, Schaar M, Garib V, Focke-Tejkl M, Li Y, Jones R, Chen H, Valenta R, Sun B. The Molecular Allergen Recognition Profile in China as Basis for Allergen-Specific Immunotherapy. Front Immunol 2021; 12:719573. [PMID: 34512644 PMCID: PMC8430339 DOI: 10.3389/fimmu.2021.719573] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 07/21/2021] [Indexed: 11/25/2022] Open
Abstract
Approximately 30% of the world population suffers from immunoglobulin-E (IgE)-mediated allergy. IgE-mediated allergy affects the respiratory tract, the skin and the gastrointestinal tract and may lead to life-threatening acute systemic manifestations such as anaphylactic shock. The symptoms of allergy are mediated by IgE-recognition of causative allergen molecules from different allergen sources. Today, molecular allergy diagnosis allows determining the disease-causing allergens to develop allergen-specific concepts for prevention and treatment of allergy. Allergen-specific preventive and therapeutic strategies include allergen avoidance, vaccination, and tolerance induction. The implementation of these preventive and therapeutic strategies requires a detailed knowledge of the relevant allergen molecules affecting a given population. China is the world´s most populous country with around 1.4 billion inhabitants and an estimated number of more than 400 million allergic patients. Research in allergy in China has dramatically increased in the last decade. We summarize in this review article what is known about the dominating allergen sources and allergen molecules in China and what further investigations could be performed to draw a molecular map of IgE sensitization for China as a basis for the implementation of systematic and rational allergen-specific preventive and therapeutic strategies to combat allergic diseases in this country.
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Affiliation(s)
- Nishelle D'souza
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Milena Weber
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Eszter Sarzsinszky
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Susanne Vrtala
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Mirela Curin
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Mirjam Schaar
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Victoria Garib
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Margarete Focke-Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Yanqiu Li
- Worg Pharmaceuticals, Hangzhou, China
| | | | - Hao Chen
- Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia.,National Research Center (NRC) Institute of Immunology Federal Medico-Biological Agency (FMBA) of Russia, Moscow, Russia.,Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Baoqing Sun
- Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Protić-Rosić I, Nešić A, Lukić I, Miljković R, Popović DM, Atanasković-Marković M, Stojanović M, Gavrović-Jankulović M. Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion. Mol Immunol 2021; 138:58-67. [PMID: 34364073 DOI: 10.1016/j.molimm.2021.06.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 05/27/2021] [Accepted: 06/22/2021] [Indexed: 11/28/2022]
Abstract
Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant β sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.
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Affiliation(s)
- Isidora Protić-Rosić
- Department of Biochemistry, Faculty of Chemistry University of Belgrade, Belgrade, Serbia
| | - Andrijana Nešić
- Department of Biochemistry, Faculty of Chemistry University of Belgrade, Belgrade, Serbia
| | - Ivana Lukić
- Department of Research and Development, Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia
| | - Radmila Miljković
- Department of Research and Development, Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia
| | - Dragan M Popović
- University of Belgrade - Institute of Chemistry, Technology and Metallurgy - National Institute of the Republic of Serbia, Belgrade, Serbia
| | - Marina Atanasković-Marković
- Department of Allergology and Pulmonology, University Children's Hospital, Medical Faculty University of Belgrade, Belgrade, Serbia
| | - Marijana Stojanović
- Department of Research and Development, Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia
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Gheerbrant H, Guillien A, Vernet R, Lupinek C, Pison C, Pin I, Demenais F, Nadif R, Bousquet J, Pickl WF, Valenta R, Bouzigon E, Siroux V. Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort. Allergy 2021; 76:2575-2586. [PMID: 33742477 DOI: 10.1111/all.14820] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 01/27/2021] [Accepted: 02/09/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class-II genomic region is a strong candidate. OBJECTIVE To assess the association between HLA class-II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules. METHODS The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class-II alleles. For each sIgE sensitization and HLA class-II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p-values were corrected for multiple comparisons (False Discovery Rate). RESULTS Most of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB1*05:01, DQA1*01:01 and DRB1*01:01, respectively). CONCLUSION Our results support the important role of HLA class-II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens.
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Affiliation(s)
- Hubert Gheerbrant
- Service Hospitalier Universitaire Pneumologie Physiologie Centre Hospitalier Universitaire Grenoble Alpes Grenoble France
- Inserm CNRS IAB Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health University Grenoble Alpes Grenoble France
| | - Alicia Guillien
- Inserm CNRS IAB Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health University Grenoble Alpes Grenoble France
| | - Raphaël Vernet
- UMRS 1124 INSERM Group of Genomic Epidemiology of Multifactorial Diseases Université de Paris Paris France
| | - Christian Lupinek
- Division of Immunopathology Department of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | - Christophe Pison
- Service Hospitalier Universitaire Pneumologie Physiologie Centre Hospitalier Universitaire Grenoble Alpes Grenoble France
- Inserm 1055 Laboratoire de Bioénergétique Fondamentale et Appliquée Grenoble France
| | - Isabelle Pin
- Inserm CNRS IAB Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health University Grenoble Alpes Grenoble France
- Department of Pediatrics Grenoble‐Alpes University Hospital Grenoble France
| | - Florence Demenais
- UMRS 1124 INSERM Group of Genomic Epidemiology of Multifactorial Diseases Université de Paris Paris France
| | - Rachel Nadif
- Université Paris‐Saclay UVSQ Univ. Paris‐Sud Inserm Équipe d'Épidémiologie respiratoire intégrative CESP Villejuif France
| | - Jean Bousquet
- Arnaud de Villeneuve University Hospital and Inserm Montpellier France
| | - Winfried F. Pickl
- Institute of Immunology Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
| | - Rudolf Valenta
- Division of Immunopathology Department of Pathophysiology and Allergy Research Center for Pathophysiology, Infectiology and Immunology Medical University of Vienna Vienna Austria
- NRC Institute of Immunology FMBA of Russia Moscow Russia
- Laboratory for Immunopathology Department of Clinical Immunology and Allergy Sechenov First Moscow State Medical University Moscow Russia
- Karl Landsteiner University of Health Sciences Krems Austria
| | - Emmanuelle Bouzigon
- UMRS 1124 INSERM Group of Genomic Epidemiology of Multifactorial Diseases Université de Paris Paris France
| | - Valérie Siroux
- Inserm CNRS IAB Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health University Grenoble Alpes Grenoble France
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Padayachee Y, Flicker S, Linton S, Cafferkey J, Kon OM, Johnston SL, Ellis AK, Desrosiers M, Turner P, Valenta R, Scadding GK. Review: The Nose as a Route for Therapy. Part 2 Immunotherapy. FRONTIERS IN ALLERGY 2021; 2:668781. [PMID: 35387044 PMCID: PMC8974912 DOI: 10.3389/falgy.2021.668781] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 05/28/2021] [Indexed: 12/12/2022] Open
Abstract
The nose provides a route of access to the body for inhalants and fluids. Unsurprisingly it has a strong immune defense system, with involvement of innate (e.g., epithelial barrier, muco- ciliary clearance, nasal secretions with interferons, lysozyme, nitric oxide) and acquired (e.g., secreted immunoglobulins, lymphocytes) arms. The lattice network of dendritic cells surrounding the nostrils allows rapid uptake and sampling of molecules able to negotiate the epithelial barrier. Despite this many respiratory infections, including SARS-CoV2, are initiated through nasal mucosal contact, and the nasal mucosa is a significant "reservoir" for microbes including Streptococcus pneumoniae, Neisseria meningitidis and SARS -CoV-2. This review includes consideration of the augmentation of immune defense by the nasal application of interferons, then the reduction of unnecessary inflammation and infection by alteration of the nasal microbiome. The nasal mucosa and associated lymphoid tissue (nasopharynx-associated lymphoid tissue, NALT) provides an important site for vaccine delivery, with cold-adapted live influenza strains (LAIV), which replicate intranasally, resulting in an immune response without significant clinical symptoms, being the most successful thus far. Finally, the clever intranasal application of antibodies bispecific for allergens and Intercellular Adhesion Molecule 1 (ICAM-1) as a topical treatment for allergic and RV-induced rhinitis is explained.
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Affiliation(s)
- Yorissa Padayachee
- Department of Respiratory Medicine, Faculty of Medicine, Imperial College Healthcare NHS Trust, Imperial College London, London, United Kingdom
| | - Sabine Flicker
- Center for Pathophysiology, Infectiology and Immunology, Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Sophia Linton
- Division of Allergy and Immunology, Department of Medicine, Queen's University, Kingston, ON, Canada
- Allergy Research Unit, Kingston Health Sciences Centre (KHSC), Kingston, ON, Canada
| | - John Cafferkey
- Department of Respiratory Medicine, Faculty of Medicine, Imperial College Healthcare NHS Trust, Imperial College London, London, United Kingdom
| | - Onn Min Kon
- Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Sebastian L. Johnston
- Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Anne K. Ellis
- Division of Allergy and Immunology, Department of Medicine, Queen's University, Kingston, ON, Canada
| | - Martin Desrosiers
- Department of Otorhinolaryngologie, The University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada
| | - Paul Turner
- Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Rudolf Valenta
- Division of Immunopathology, Medical University of Vienna, Vienna, Austria
| | - Glenis Kathleen Scadding
- Royal National Ear Nose and Throat Hospital, University College London Hospitals NHS Foundation Trust, London, United Kingdom
- Division of Infection and Immunity, Faculty of Medical Sciences, University College London, London, United Kingdom
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44
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Cloning and immunobiochemical analyses on recombinant chymopapain allergen Cari p 2 showing pollen-fruit cross-reaction. Mol Immunol 2021; 137:42-51. [PMID: 34214828 DOI: 10.1016/j.molimm.2021.06.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 05/11/2021] [Accepted: 06/15/2021] [Indexed: 11/23/2022]
Abstract
Papaya is reported to trigger food and respiratory allergy. Here, we identified chymopapain Cari p 2 as an allergen that can sensitize atopic individuals through fruit consumption followed by respiratory hazards through pollen exposure. Recombinant Cari p 2 displayed IgE-reactivity with 78% of papaya allergic sera. rCari p 2 also displayed allergenic activity through basophil degranulation. rCari p 2 is correctly folded and showed irreversible denaturation in the melting curve. rCari p 2 displayed IgE-cross-reactivity with homologous cysteine proteases from kiwi and pineapple. Cari p 2 transcript was also detected in papaya pulps. rCari p 2 was resistant to pepsin digestion and retained IgE-reactivity after 60 minutes of pepsin digestion. In mouse model, rCari p 2 was found to elicit inflammatory responses in the lung and gastrointestinal epithelium. Hence, Cari p 2 is a newly characterized allergen with diagnostic and immunotherapeutic potential for managing allergic disorders in papaya sensitized individuals.
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Curin M, Huang HJ, Garmatiuk T, Gutfreund S, Resch-Marat Y, Chen KW, Fauland K, Keller W, Zieglmayer P, Zieglmayer R, Lemell P, Horak F, Hemmer W, Focke-Tejkl M, Flicker S, Vrtala S, Valenta R. IgE Epitopes of the House Dust Mite Allergen Der p 7 Are Mainly Discontinuous and Conformational. Front Immunol 2021; 12:687294. [PMID: 34220841 PMCID: PMC8241568 DOI: 10.3389/fimmu.2021.687294] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 04/30/2021] [Indexed: 11/13/2022] Open
Abstract
Background Several studies indicate that Der p 7 is an important and clinically relevant allergen of Dermatophagoides pteronyssinus which should be included in vaccines for treatment of house dust mite (HDM) allergy. Aim of this study was to characterize the IgE epitopes of Der p 7. Methods Recombinant Der p 7 was expressed and purified, analyzed for fold by circular dichroism and tested for its allergenic activity by basophil activation. Seven overlapping, surface-exposed peptides (P1–P7) with a length of 27 to 37 amino acids, which spanned the Der p 7 sequence, were synthesized and tested for IgE reactivity and allergenic activity by basophil activation assay. Carrier-bound peptides were studied for their ability to induce allergen-specific IgG antibodies in rabbits. Peptide-specific antibodies were used to inhibit allergic patients` IgE binding to Der p 7 by ELISA for mapping of IgE epitopes. Results rDer p 7 showed high allergenic activity comparable with Der p 5, Der p 21, and Der p 23. None of the seven tested peptides showed any IgE reactivity or allergenic activity when tested with HDM- allergic patients indicating lack of sequential IgE epitopes on Der p 7. IgE inhibition experiments using anti-peptide specific IgGs and molecular modeling enabled us to identify discontinuous, conformational IgE epitopes of Der p 7. Conclusion and Clinical Relevance IgE epitopes of Der p 7 belong to the conformational and discontinuous type whereas sequential Der p 7 peptides lack IgE reactivity. It should thus be possible to construct hypoallergenic vaccines for Der p 7 based on carrier-bound allergen peptides.
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Affiliation(s)
- Mirela Curin
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Huey-Jy Huang
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Tetiana Garmatiuk
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Sandra Gutfreund
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Yvonne Resch-Marat
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Kuan-Wei Chen
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Kerstin Fauland
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | - Walter Keller
- Institute of Molecular Biosciences, University of Graz, Graz, Austria
| | - Petra Zieglmayer
- Vienna Challenge Chamber, Vienna, Austria.,Karl Landsteiner University of Health Sciences, Krems, Austria
| | | | | | | | | | - Margarete Focke-Tejkl
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Sabine Flicker
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Susanne Vrtala
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,Karl Landsteiner University of Health Sciences, Krems, Austria.,Department of Clinical Immunology and Allergy, Sechenov First State Medical University, Moscow, Russia.,NRC Institute of Immunology FMBA of Russia, Moscow, Russia
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46
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Popescu FD, Ganea CS, Panaitescu C, Vieru M. Molecular diagnosis in cat allergy. World J Methodol 2021; 11:46-60. [PMID: 34026578 PMCID: PMC8127422 DOI: 10.5662/wjm.v11.i3.46] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Revised: 02/22/2021] [Accepted: 05/10/2021] [Indexed: 02/06/2023] Open
Abstract
Domestic cats represent one of the most common sources of indoor allergens. All over the world, many households own cats, whose allergens are persistent and widespread. Cat allergy itself is frequent, and its symptoms vary from rhinoconjunctivitis to life-threatening asthma. In vitro diagnosis using precision medicine allergy immunoassays is important because natural cat dander extracts may differ in quality and quantity of some of the individual allergen components and other molecules. In the component-resolved diagnosis of cat allergy, singleplex and multiplex specific immunoglobulin (Ig) E assays include use of the cat-specific major allergen, secretoglobin Fel d 1 (as a species-specific molecule), other allergen components (such as lipocalins Fel d 4, cross-reacting with other animal similar molecules, and Fel d 7, present in small quantities in natural extracts), and serum albumin Fel d 2 (related to the cat-pork syndrome). IgA Fel d 5 and IgM Fel d 6 are not available as allergen components in the current commercial IgE immunoassays, but they may impair the in vitro diagnostic evaluation of cat allergy because galactose-α1,3-galactose is an IgE-binding epitope of these native feline allergens. The benefits of molecular-based cat allergy diagnosis are continually evaluated, as the role of recombinant allergen components already known is detailed and new other molecules of interest may be discovered in the future.
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Affiliation(s)
- Florin-Dan Popescu
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
| | - Carmen Saviana Ganea
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
| | - Carmen Panaitescu
- Department III Functional Sciences, Physiology Discipline, “Victor Babes” University of Medicine and Pharmacy, Timișoara 300041, Romania
- Center for Gene and Cell Therapies in Cancer Treatment OncoGen-SCJUPB Timisoara, Timișoara 300041, Romania
| | - Mariana Vieru
- Department of Allergology and Clinical Immunology, “Nicolae Malaxa” Clinical Hospital, Bucharest 022441, Romania
- Department of Allergology, “Carol Davila” University of Medicine and Pharmacy, Bucharest 022441, Romania
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47
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Cui X, Li X, Xu Z, Guan X, Ma J, Ding D, Zhang W. Fabrication and Characterization of Chitosan/Poly(Lactic-Co-glycolic Acid) Core-Shell Nanoparticles by Coaxial Electrospray Technology for Dual Delivery of Natamycin and Clotrimazole. Front Bioeng Biotechnol 2021; 9:635485. [PMID: 33748084 PMCID: PMC7973235 DOI: 10.3389/fbioe.2021.635485] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 01/26/2021] [Indexed: 02/02/2023] Open
Abstract
Natamycin (NAT) is the drug of choice for the treatment of fungal keratitis (FK). However, its inherent shortcomings, such as poor solubility, high dosing frequency, and long treatment cycle, need to be urgently addressed by designing a new delivery to widen its clinical utility. Growing research has confirmed that clotrimazole (CLZ) plays a significant role in fungal growth inhibition. Hence, coaxial electrospray (CO-ES) technology is used herein to prepare nano-systems with an average hydrodynamic particle size of 309-406 nm for the co-delivery of NAT and CLZ in chitosan (CTS) and poly(lactic-co-glycolic acid) (PLGA). The resulting NAT/CLZ@CTS/PLGA formulations were characterized by a transmission electron microscope (TEM) and in vitro release test. The results show that the formulations had obvious core-shell structures, uniform particle distribution, and also can sustain the release of drugs over 36 h. Furthermore, in vitro hemolysis, in vivo corneal irritation test, local allergenic test, and antifungal activity analyses are performed to evaluate the safety and efficiency of the formulations. Thus, good biosafety along with a significant anti-candidiasis effect are found in the NAT/CLZ@CTS/PLGA nanoparticles (NPs). Taken together, the results suggest that this design may provide a promising drug delivery system and a new option for the treatment of FK.
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Affiliation(s)
- Xiaoming Cui
- College of Pharmacy, Weifang Medical University, Weifang, China
| | - Xiaoli Li
- Department of Pharmacy, Weifang Traditional Chinese Hospital, Weifang, China
| | - Zhilu Xu
- College of Pharmacy, Weifang Medical University, Weifang, China
| | - Xiuwen Guan
- College of Pharmacy, Weifang Medical University, Weifang, China.,Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, China.,Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang, China
| | - Jinlong Ma
- College of Pharmacy, Weifang Medical University, Weifang, China.,Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, China.,Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang, China
| | - Dejun Ding
- College of Pharmacy, Weifang Medical University, Weifang, China.,Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, China.,Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang, China
| | - Weifen Zhang
- College of Pharmacy, Weifang Medical University, Weifang, China.,Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang, China.,Shandong Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang, China
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Huang HJ, Campana R, Akinfenwa O, Curin M, Sarzsinszky E, Karsonova A, Riabova K, Karaulov A, Niespodziana K, Elisyutina O, Fedenko E, Litovkina A, Smolnikov E, Khaitov M, Vrtala S, Schlederer T, Valenta R. Microarray-Based Allergy Diagnosis: Quo Vadis? Front Immunol 2021; 11:594978. [PMID: 33679689 PMCID: PMC7928321 DOI: 10.3389/fimmu.2020.594978] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 12/08/2020] [Indexed: 12/24/2022] Open
Abstract
More than 30% of the world population suffers from allergy. Allergic individuals are characterized by the production of immunoglobulin E (IgE) antibodies against innocuous environmental allergens. Upon allergen recognition IgE mediates allergen-specific immediate and late-phase allergic inflammation in different organs. The identification of the disease-causing allergens by demonstrating the presence of allergen-specific IgE is the key to precision medicine in allergy because it allows tailoring different forms of prevention and treatment according to the sensitization profiles of individual allergic patients. More than 30 years ago molecular cloning started to accelerate the identification of the disease-causing allergen molecules and enabled their production as recombinant molecules. Based on recombinant allergen molecules, molecular allergy diagnosis was introduced into clinical practice and allowed dissecting the molecular sensitization profiles of allergic patients. In 2002 it was demonstrated that microarray technology allows assembling large numbers of allergen molecules on chips for the rapid serological testing of IgE sensitizations with small volumes of serum. Since then microarrayed allergens have revolutionized research and diagnosis in allergy, but several unmet needs remain. Here we show that detection of IgE- and IgG-reactivity to a panel of respiratory allergens microarrayed onto silicon elements is more sensitive than glass-based chips. We discuss the advantages of silicon-based allergen microarrays and how this technology will allow addressing hitherto unmet needs in microarray-based allergy diagnosis. Importantly, it described how the assembly of silicon microarray elements may create different microarray formats for suiting different diagnostic applications such as quick testing of single patients, medium scale testing and fully automated large scale testing.
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Affiliation(s)
- Huey-Jy Huang
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Raffaela Campana
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Oluwatoyin Akinfenwa
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Mirela Curin
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Eszter Sarzsinszky
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Antonina Karsonova
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Ksenja Riabova
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Alexander Karaulov
- Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia
| | - Katarzyna Niespodziana
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Olga Elisyutina
- Department of Allergology and Clinical Immunology, NRC Institute of Immunology FMBA of Russia, Moscow, Russia
| | - Elena Fedenko
- Department of Allergology and Clinical Immunology, NRC Institute of Immunology FMBA of Russia, Moscow, Russia
| | - Alla Litovkina
- Department of Allergology and Clinical Immunology, NRC Institute of Immunology FMBA of Russia, Moscow, Russia
| | - Evgenii Smolnikov
- Department of Allergology and Clinical Immunology, NRC Institute of Immunology FMBA of Russia, Moscow, Russia
| | - Musa Khaitov
- Department of Allergology and Clinical Immunology, NRC Institute of Immunology FMBA of Russia, Moscow, Russia
| | - Susanne Vrtala
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Thomas Schlederer
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.,Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, Sechenov First Moscow State Medical University, Moscow, Russia.,Department of Allergology and Clinical Immunology, NRC Institute of Immunology FMBA of Russia, Moscow, Russia.,Karl Landsteiner University of Health Sciences, Krems, Austria
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49
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Elisyutina O, Lupinek C, Fedenko E, Litovkina A, Smolnikov E, Ilina N, Kudlay D, Shilovskiy I, Valenta R, Khaitov M. IgE-reactivity profiles to allergen molecules in Russian children with and without symptoms of allergy revealed by micro-array analysis. Pediatr Allergy Immunol 2021; 32:251-263. [PMID: 32869350 PMCID: PMC7891667 DOI: 10.1111/pai.13354] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 06/26/2020] [Accepted: 08/18/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND The analysis of longitudinal birth cohorts with micro-arrayed allergen molecules has provided interesting information about the evolution of IgE sensitization in children. However, so far no cross-sectional study has been performed comparing IgE sensitization profiles in children with and without symptoms of allergy. Furthermore, no data are available regarding molecular IgE sensitization profiles in children from Russia. METHODS We recruited two groups of age- and gender-matched children, one (Group 1: n = 103; 12.24 ± 2.23 years; male/female: 58/45) with symptoms and a second (Group 2: n = 97; 12.78 ± 2.23 years; male/female: 53/44), without symptoms of allergy according to international ISAAC questionnaire. Children were further studied regarding symptoms of allergy (rhinitis, asthma, atopic dermatitis) according to international guidelines, and skin prick testing with a panel of aeroallergen extracts was performed before sera were analyzed in an investigator-blinded manner for IgE specific to more than 160 micro-arrayed allergen molecules using ImmunoCAP ISAC technology. RESULTS IgE sensitization = or >0.3 ISU to at least one of the micro-arrayed allergen molecules was found in 100% of the symptomatic children and in 36% of the asymptomatic children. Symptomatic and asymptomatic children showed a comparable IgE sensitization profile; however, frequencies of IgE sensitization and IgE levels to the individual allergen molecules were higher in the symptomatic children. Aeroallergen sensitization was dominated by sensitization to major birch pollen allergen, Bet v 1, and major cat allergen, Fel d 1. Food allergen sensitization was due to cross-sensitization to PR10 pollen and food allergens whereas genuine peanut sensitization was absent. CONCLUSION This is the first study analyzing molecular IgE sensitization profiles to more than 160 allergen molecules in children with and without symptoms of allergy. It detects similar molecular IgE sensitization profiles in symptomatic and asymptomatic children and identifies Bet v 1 and Fel d 1 as the predominant respiratory allergen molecules and PR10 proteins as the major food allergens and absence of genuine peanut allergy in Moscow region (Russia).
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Affiliation(s)
| | - Christian Lupinek
- Division of ImmunopathologyDepartment of Pathophysiology and Allergy ResearchCentre for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
| | - Elena Fedenko
- NRC Institute of Immunology FMBA of RussiaMoscowRussia
| | | | | | | | - Dmitry Kudlay
- NRC Institute of Immunology FMBA of RussiaMoscowRussia
| | | | - Rudolf Valenta
- NRC Institute of Immunology FMBA of RussiaMoscowRussia
- Division of ImmunopathologyDepartment of Pathophysiology and Allergy ResearchCentre for Pathophysiology, Infectiology and ImmunologyMedical University of ViennaViennaAustria
- Sechenov First State Medical UniversityMoscowRussia
- Karl Landsteiner University for Health SciencesKremsAustria
| | - Musa Khaitov
- NRC Institute of Immunology FMBA of RussiaMoscowRussia
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50
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Akinfenwa O, Rodríguez-Domínguez A, Vrtala S, Valenta R, Campana R. Novel vaccines for allergen-specific immunotherapy. Curr Opin Allergy Clin Immunol 2021; 21:86-99. [PMID: 33369572 PMCID: PMC7810419 DOI: 10.1097/aci.0000000000000706] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE OF REVIEW Allergen-specific immunotherapy (AIT) is a highly economic, effective and disease-modifying form of allergy treatment but requires accurate prescription and monitoring. New molecular approaches are currently under development to improve AIT by reducing treatment-related side effects, cumbersome protocols and patients' compliance. We review the current advances regarding refined diagnosis for prescription and monitoring of AIT and the development of novel molecular vaccines for AIT. Finally, we discuss prophylactic application of AIT. RECENT FINDINGS There is evidence that molecular allergy diagnosis not only assists in the prescription and monitoring of AIT but also allows a refined selection of patients to increase the likelihood of treatment success. New data regarding the effects of AIT treatment with traditional allergen extracts by alternative routes have become available. Experimental approaches for AIT, such as virus-like particles and cell-based treatments have been described. New results from clinical trials performed with recombinant hypoallergens and passive immunization with allergen-specific antibodies highlight the importance of allergen-specific IgG antibodies for the effect of AIT and indicate opportunities for preventive allergen-specific vaccination. SUMMARY Molecular allergy diagnosis is useful for the prescription and monitoring of AIT and may improve the success of AIT. Results with molecular allergy vaccines and by passive immunization with allergen-specific IgG antibodies indicate the importance of allergen-specific IgG capable of blocking allergen recognition by IgE and IgE-mediated allergic inflammation as important mechanism for the success of AIT. New molecular vaccines may pave the road towards prophylactic allergen-specific vaccination.
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Affiliation(s)
- Oluwatoyin Akinfenwa
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Azahara Rodríguez-Domínguez
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Susanne Vrtala
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Rudolf Valenta
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- NRC Institute of Immunology FMBA of Russia
- Laboratory for Immunopathology, Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, Moscow, Russia
- Karl Landsteiner University of Health Sciences, Krems, Austria
| | - Raffaela Campana
- Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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