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Vaz-Rodrigues R, Rafael M, Carniato D, de la Fuente J. Public perspectives on tick bite exposure, healthcare visits and associated allergies in iberia. Ann Med 2025; 57:2499028. [PMID: 40317252 PMCID: PMC12051554 DOI: 10.1080/07853890.2025.2499028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 04/01/2025] [Accepted: 04/04/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND Tick bites and tick-borne diseases (TBDs) are a worldwide concern, with growing evidence of an ongoing spread and emergence of new cases. This study applied a participatory citizen science across Spain and Portugal to gather public perspectives on the impact of tick bites, the presence of TBDs and a potential connection with the α-Gal syndrome (AGS). METHODS Data collected from the questionnaire (380 participants) was geographically represented using QGIS Geographic Information System and fitted into multiple generalized linear models (GLMs). Statistical analysis identified factors influencing the occurrence of local skin reactions post-tick bite, AGS-compatible symptoms and visits to health centers following tick exposure. RESULTS Results showed that the probability of developing localized skin reactions to tick bites rises with increasing age (χ2 = 0.006, p < 0.05), the occurrence of multiple bites (χ2 = 0.006, p = 0.063) and among individuals bitten in the center-north part of the peninsula (χ2 = 0.006, p = 0.058). Seeking medical care following tick bite was reported by 21.6% of respondents, being more common in first-time bite cases (χ2 = 0.002, p < 0.01), men (χ2 = 0.002, p < 0.01) or individuals presenting localized skin symptoms (χ2 = 0.002, p < 0.05). Although 38 inquiries (10.0%) showed signs of AGS, only 3 had received a formal diagnosis, with the odds of developing this disease marginally rising with advancing age (χ2 = 0.215, p = 0.066). CONCLUSIONS This study provides valuable insights that should be considered to improve TBDs surveillance and diagnostic strategies, as well as developing preventive measures to reduce tick bite exposure and TBD cases.Key MessagesDeveloping local skin reactions to tick bites increases with age, multiple bites and in individuals bitten in central-northern Iberia.Seeking medical care following a tick bite is more common in first-time bite cases, men or individuals with local skin symptoms.Although 38 inquiries (10.0%) showed signs of AGS, only 3 were formally diagnosed, with risk increasing with age.
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Affiliation(s)
- Rita Vaz-Rodrigues
- SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain
| | - Marta Rafael
- SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain
| | - Davide Carniato
- Department of Veterinary Medicine, University of Sassari, Sassari, Italy
| | - José de la Fuente
- SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain
- Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA
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Vaz‐Rodrigues R, de la Fuente J. Is Zebrafish a Good Model for the Alpha-Gal Syndrome? FASEB J 2025; 39:e70602. [PMID: 40317760 PMCID: PMC12047429 DOI: 10.1096/fj.202500687r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 04/04/2025] [Accepted: 04/24/2025] [Indexed: 05/07/2025]
Abstract
The alpha-Gal syndrome (AGS) is an underdiagnosed tick-borne allergy characterized by both immediate and delayed IgE-mediated anaphylactic reactions to the galactose-alpha-1,3-galactose (alpha-Gal) epitope. Common manifestations include gastrointestinal, cutaneous, and respiratory symptoms appearing 2-6 h after the consumption of mammalian meat or derived products. Zebrafish (Danio rerio) are emerging as essential animal models in biomedical studies, due to their anatomical, genetic, and physiological similarities to humans, with significant applications in toxicology, behavioral research, oncology, and inflammation studies. The mechanisms associated with AGS are sustained by studies in the humanized α1,3GalT-KO C57BL/6 mouse (Mus musculus) and zebrafish animal models for the production of anti-alpha-Gal antibodies in response to tick saliva, the development of allergic reactions in animals sensitized with tick protein extracts following mammalian meat consumption, and the identification of immune mechanisms. The immune mechanisms characterized in both models are associated with a skewed type 2 immune response, triggering Toll-Like receptor (TLR) signaling pathways, IL-4 production, and humoral activity. These results support the use of both models rather than a single one for a more comprehensive characterization of AGS-associated immune mechanisms. In this study, we focused on the use of zebrafish as a model for biomedicine research in immunity, infectious, and allergic diseases, with a particular emphasis on the AGS and the identification of candidate therapeutic interventions. Based on insights from multiple studies, we concluded that zebrafish is a suitable model for studying the AGS, considering the addressed limitations and in combination with the α1,3GalT-KO mouse model.
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Affiliation(s)
- Rita Vaz‐Rodrigues
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC‐CSIC‐UCLM‐JCCMCiudad RealSpain
| | - José de la Fuente
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC‐CSIC‐UCLM‐JCCMCiudad RealSpain
- Department of Veterinary Pathobiology, College of Veterinary MedicineOklahoma State UniversityStillwaterOklahomaUSA
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Raulf M, Annesi-Maesano I. Occupational allergy and climate change. Curr Opin Allergy Clin Immunol 2025; 25:83-87. [PMID: 39869536 DOI: 10.1097/aci.0000000000001060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2025]
Abstract
PURPOSE OF REVIEW Climate change influences working conditions in various ways, affecting employee health and safety across different sectors. Climatic factors like rising temperatures, increased UV radiation, and more frequent extreme weather events pose risks to in both indoor and outdoor workers. Allergic diseases of the respiratory tract and the skin may emerge due to climate change. This review summarizes current aspects of both direct and indirect consequences of climate change and associated exposures in diverse work environments, focusing on occupational allergies. RECENT FINDINGS Outdoor workers, in particular, are increasing susceptible to ubiquitous pollen allergens. Additionally, they may experience climate-related increases in allergens typically associated with specific workplaces, such as Cryptostroma corticale . Changes in production processes, along with altered workplaces exposures, can lead to new sensitizations and trigger allergies, representing indirect consequences of climate change. Furthermore, lifestyle changes aimed to promoting climate protection and sustainability (e.g. the introduction of insects as a protein source or using enzymes), may also contribute to the emergence of new allergens. SUMMARY The emergence of new occupational sensitization sources from novel or modified allergen exposures must be addressed within the framework of workplace safety and health, necessitating proactive measures to safeguard workers and mitigate risks.
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Affiliation(s)
- Monika Raulf
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Germany
| | - Isabella Annesi-Maesano
- Department of Pulmonology, Allergy and Thoracic Oncology, University Hospital of Montpellier, Montpellier, France
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Darsow U, Gelincik A, Jappe U, Platts-Mills TA, Ünal D, Biedermann T. Algorithms in allergy: An algorithm for alpha-Gal syndrome diagnosis and treatment, 2024 update. Allergy 2024; 79:3169-3172. [PMID: 39175257 DOI: 10.1111/all.16291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/25/2024] [Accepted: 08/16/2024] [Indexed: 08/24/2024]
Affiliation(s)
- U Darsow
- Department of Dermatology and Allergy Biederstein, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
| | - A Gelincik
- Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - U Jappe
- Division of Clinical and Molecular Allergology, Research Center Borstel, Airway Research, Center North (ARCN), Member of the German Center for Lung Research, Borstel, Germany
- Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Luebeck, Luebeck, Germany
| | - T A Platts-Mills
- School of Medicine, Department of Medicine, Division of Asthma, Allergy, and Immunology, University of Virginia, Charlottesville, Virginia, USA
| | - D Ünal
- Division of Immunology and Allergic Diseases, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - T Biedermann
- Department of Dermatology and Allergy Biederstein, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany
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Su J, Tong Z, Feng Z, Wu S, Zhou F, Li R, Chen W, Ye Z, Guo Y, Yao S, Yu X, Chen Q, Chen L. Protective effects of DcR3-SUMO on lipopolysaccharide-induced inflammatory cells and septic mice. Int J Biol Macromol 2024; 275:133703. [PMID: 38986982 DOI: 10.1016/j.ijbiomac.2024.133703] [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: 05/14/2024] [Revised: 07/03/2024] [Accepted: 07/04/2024] [Indexed: 07/12/2024]
Abstract
Despite the high mortality rate associated with sepsis, no specific drugs are available. Decoy receptor 3 (DcR3) is now considered a valuable biomarker and therapeutic target for managing inflammatory conditions. DcR3-SUMO, an analog of DcR3, has a simple production process and high yield. However, its precise underlying mechanisms in sepsis remain unclear. This study investigated the protective effects of DcR3-SUMO on lipopolysaccharide (LPS)-induced inflammatory cells and septic mice. We evaluated the effects of DcR3 intervention and overexpression on intracellular inflammatory cytokine levels in vitro. DcR3-SUMO significantly reduced cytokine levels within inflammatory cells, and notably increased DcR3 protein and mRNA levels in LPS-induced septic mice, confirming its anti-inflammatory efficacy. Our in vitro and in vivo results demonstrated comparable anti-inflammatory effects between DcR3-SUMO and native DcR3. DcR3-SUMO protein administration in septic mice notably enhanced tissue morphology, decreased sepsis scores, and elevated survival rates. Furthermore, DcR3-SUMO treatment effectively lowered inflammatory cytokine levels in the serum, liver, and lung tissues, and mitigated the extent of tissue damage. AlphaFold3 structural predictions indicated that DcR3-SUMO, similar to DcR3, effectively interacts with the three pro-apoptotic ligands, namely TL1A, LIGHT, and FasL. Collectively, DcR3-SUMO and DcR3 exhibit comparable anti-inflammatory effects, making DcR3-SUMO a promising therapeutic agent for sepsis.
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Affiliation(s)
- Jingqian Su
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou 350117, China.
| | - Zhiyong Tong
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou 350117, China
| | - Zhihua Feng
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou 350117, China
| | - Shun Wu
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou 350117, China
| | - Fen Zhou
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou 350117, China
| | - Rui Li
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Wenzhi Chen
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou 350117, China
| | - Zhen Ye
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Yu Guo
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Shun Yao
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Xing Yu
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China
| | - Qi Chen
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou 350117, China.
| | - Long Chen
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai 200040, China.
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Peterson L, Yacoub MH, Ayares D, Yamada K, Eisenson D, Griffith BP, Mohiuddin MM, Eyestone W, Venter JC, Smolenski RT, Rothblatt M. Physiological basis for xenotransplantation from genetically modified pigs to humans. Physiol Rev 2024; 104:1409-1459. [PMID: 38517040 PMCID: PMC11390123 DOI: 10.1152/physrev.00041.2023] [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: 10/26/2023] [Revised: 03/06/2024] [Accepted: 03/14/2024] [Indexed: 03/23/2024] Open
Abstract
The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning that are now being harnessed to enhance the suitability of pig organs for xenotransplantation into humans. Using organs sourced from pigs with multiple gene deletions and human transgene insertions, investigators have overcome formidable immunological and physiological barriers in pig-to-nonhuman primate (NHP) xenotransplantation and achieved prolonged pig xenograft survival. These studies informed the design of Revivicor's (Revivicor Inc, Blacksburg, VA) genetically engineered pigs with 10 genetic modifications (10 GE) (including the inactivation of 4 endogenous porcine genes and insertion of 6 human transgenes), whose hearts and kidneys have now been studied in preclinical human xenotransplantation models with brain-dead recipients. Additionally, the first two clinical cases of pig-to-human heart xenotransplantation were recently performed with hearts from this 10 GE pig at the University of Maryland. Although this review focuses on xenotransplantation of hearts and kidneys, multiple organs, tissues, and cell types from genetically engineered pigs will provide much-needed therapeutic interventions in the future.
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Affiliation(s)
- Leigh Peterson
- United Therapeutics Corporation, Silver Spring, Maryland, United States
| | | | - David Ayares
- United Therapeutics Corporation, Silver Spring, Maryland, United States
| | - Kazuhiko Yamada
- Department of Surgery, Division of Transplantation, Johns Hopkins Medicine, Baltimore, Maryland, United States
| | - Daniel Eisenson
- Department of Surgery, Division of Transplantation, Johns Hopkins Medicine, Baltimore, Maryland, United States
| | - Bartley P Griffith
- University of Maryland Medical Center, Baltimore, Maryland, United States
| | | | - Willard Eyestone
- United Therapeutics Corporation, Silver Spring, Maryland, United States
| | - J Craig Venter
- J. Craig Venter Institute, Rockville, Maryland, United States
| | | | - Martine Rothblatt
- United Therapeutics Corporation, Silver Spring, Maryland, United States
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Su J, Chen W, Zhou F, Li R, Tong Z, Wu S, Ye Z, Zhang Y, Lin B, Yu X, Guan B, Feng Z, Chen K, Chen Q, Chen L. Inhibitory mechanisms of decoy receptor 3 in cecal ligation and puncture-induced sepsis. mBio 2024; 15:e0052124. [PMID: 38700314 PMCID: PMC11237498 DOI: 10.1128/mbio.00521-24] [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: 02/21/2024] [Accepted: 04/02/2024] [Indexed: 05/05/2024] Open
Abstract
Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies. IMPORTANCE Sepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.
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Affiliation(s)
- Jingqian Su
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
| | - Wenzhi Chen
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
- Institute of Edible Fungi, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
| | - Fen Zhou
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
| | - Rui Li
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhiyong Tong
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
| | - Shun Wu
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
| | - Zhen Ye
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai, China
| | - Yichao Zhang
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai, China
| | - Ben Lin
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai, China
| | - Xing Yu
- Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Biyun Guan
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
| | - Zhihua Feng
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
| | - Kunsen Chen
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
| | - Qi Chen
- Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou, China
| | - Long Chen
- Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai, China
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DuToit G, Smith P, Muraro A, Fox AT, Roberts G, Ring J, Worm M. Identifying patients at risk of anaphylaxis. World Allergy Organ J 2024; 17:100904. [PMID: 38966605 PMCID: PMC11223123 DOI: 10.1016/j.waojou.2024.100904] [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: 05/31/2023] [Revised: 03/31/2024] [Accepted: 04/05/2024] [Indexed: 07/06/2024] Open
Abstract
Anaphylaxis is an acute, potentially fatal, systemic hypersensitivity reaction that warrants prompt diagnosis and management. It continues to be challenging to anticipate who may be at risk of a severe, life-threatening allergic reaction. Anaphylaxis can be caused by a range of allergens, such as certain foods, medications, latex, insect stings, etc. Cofactors that augment the severity of clinical symptoms and increase the risk of poor outcomes include exercise, stress, infectious diseases, underlying mast cell disease, active allergic disease such as asthma, advanced age, intake of certain medications, history of previous anaphylaxis, and delayed or missed administration of adrenaline. According to the European Anaphylaxis Registry, food is the major elicitor of anaphylaxis, especially eggs, cow milk, and nuts, in children and adolescents. Reaction to insect venom has also been noted in young adulthood. Early recognition of signs and symptoms and prompt treatment are crucial in anaphylaxis management to avoid serious and even fatal outcomes. It is crucial for both individuals and clinicians to identify the cause of anaphylaxis. Biomarkers of anaphylaxis, such as histamine, tryptase, platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, CCL-2, hsa-miR-451a, may be useful in diagnosis and management. The purpose of this review article is to present a comprehensive overview of current evidence and expert opinions regarding the risk factors that predispose individuals to anaphylaxis. Additionally, it provides insights into potential biomarkers and genetic markers for accurate diagnosis and management. This review underscores the significance of expert guidance in enhancing patient outcomes and enabling self-management of anaphylactic episodes.
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Affiliation(s)
- George DuToit
- Pediatric Allergy King's College London and Guy's and St Thomas', London, United Kingdom
| | - Pete Smith
- Clinical School of Medicine, Griffith University, Southport, Queensland, Australia
| | - Antonella Muraro
- Food Allergy Referral Centre, Department of Woman and Child Health, Padua University Hospital, Padua, Italy
| | - Adam T. Fox
- Children's Allergy Service, Guy's and St Thomas' Hospitals NHS Foundation Trust, Westminster Bridge, London, United Kingdom
| | - Graham Roberts
- University of Southampton, Pediatric Allergy & Respiratory Medicine, Tremona Road, Southampton, United Kingdom
| | - Johannes Ring
- Technical University Munich (TUM), Dept Dermatology Allergology Biederstein, Germany
| | - Margitta Worm
- Allergologie und Immunologie, Klinik für Dermatologie, Venerologie und Allergologie, Campus Charité Mitte, Universitätsmedizin Berlin, Berlin, Germany
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Sharma SR, Choudhary SK, Vorobiov J, Commins SP, Karim S. Tick bite-induced alpha-gal syndrome and immunologic responses in an alpha-gal deficient murine model. Front Immunol 2024; 14:1336883. [PMID: 38390396 PMCID: PMC10882631 DOI: 10.3389/fimmu.2023.1336883] [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: 11/11/2023] [Accepted: 12/26/2023] [Indexed: 02/24/2024] Open
Abstract
Introduction Alpha-Gal Syndrome (AGS) is a delayed allergic reaction due to specific IgE antibodies targeting galactose-α-1,3-galactose (α-gal), a carbohydrate found in red meat. This condition has gained significant attention globally due to its increasing prevalence, with more than 450,000 cases estimated just in the United States alone. Previous research has established a connection between AGS and tick bites, which sensitize individuals to α-gal antigens and elevate the levels of specific IgE. However, the precise mechanism by which tick bites influence the host's immune system and contribute to the development of AGS remains poorly understood. This study investigates various factors related to ticks and the host associated with the development of AGS following a tick bite, using mice with a targeted disruption of alpha-1,3-galactosyltransferase (AGKO) as a model organism. Methods Lone-star tick (Amblyomma americanum) and gulf-coast tick (Amblyomma maculatum) nymphs were used to sensitize AGKO mice, followed by pork meat challenge. Tick bite site biopsies from sensitized and non-sensitized mice were subjected to mRNA gene expression analysis to assess the host immune response. Antibody responses in sensitized mice were also determined. Results Our results showed a significant increase in the total IgE, IgG1, and α-gal IgG1 antibodies titers in the lone-star tick-sensitized AGKO mice compared to the gulf-coast tick-sensitized mice. Pork challenge in Am. americanum -sensitized mice led to a decline in body temperature after the meat challenge. Gene expression analysis revealed that Am. americanum bites direct mouse immunity toward Th2 and facilitate host sensitization to the α-gal antigen. Conclusion This study supports the hypothesis that specific tick species may increase the risk of developing α-gal-specific IgE and hypersensitivity reactions or AGS, thereby providing opportunities for future research on the mechanistic role of tick and host-related factors in AGS development.
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Affiliation(s)
- Surendra Raj Sharma
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
| | - Shailesh K. Choudhary
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Julia Vorobiov
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Scott P. Commins
- Department of Medicine and Pediatrics, University of North Carolina, Chapel Hill, NC, United States
| | - Shahid Karim
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS, United States
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10
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Gan Y, Lippold S, Stobaugh J, Schöneich C, Yang F. Expanding the structural resolution of glycosylation microheterogeneity in therapeutic proteins by salt-free hydrophilic interaction liquid chromatography tandem mass spectrometry. MAbs 2024; 16:2395503. [PMID: 39192481 PMCID: PMC11364061 DOI: 10.1080/19420862.2024.2395503] [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: 05/16/2024] [Revised: 08/16/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024] Open
Abstract
Glycosylation affects the safety and efficacy of therapeutic proteins and is often considered a critical quality attribute (CQA). Therefore, it is important to identify and quantify glycans during drug development. Glycosylation is a highly complex post-translational modification (PTM) due to its structural heterogeneity, i.e. glycosylation site occupancy, glycan compositions, modifications, and isomers. Current analytical tools compromise either structural resolution or site specificity. Hydrophilic interaction liquid chromatography-fluorescence-mass spectrometry (HILIC-FLR-MS) is the gold standard for structural analysis of released glycans, but lacks information on site specificity and occupation. However, HILIC-FLR-MS often uses salt in the solvent, which impairs analysis robustness and sensitivity. Site-specific glycosylation analysis via glycopeptides, upon proteolytic digestion, is commonly performed by reversed-phase liquid chromatography-tandem mass spectrometry (RPLC-MS/MS), but provides only compositional and limited structural glycan information. In this study, we introduce a salt-free, glycopeptide-based HILIC-tandem mass spectrometry (HILIC-MS/MS) method that provides glycan identification, glycan isomer separation and site-specific information simultaneously. Moreover, HILIC-MS/MS demonstrated comparable relative quantification results as released glycan HILIC-FLR-MS. Further, our new method improves the retention of hydrophilic peptides, allowing simultaneous analysis of important CQAs such as deamidation in antibodies. The developed method offers a valuable tool to streamline the site-specific glycosylation analysis of glycoproteins, which is particularly important for the expanding landscape of novel therapeutic formats in the biopharmaceutical industry.
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Affiliation(s)
- Yutian Gan
- Protein Analytical Chemistry, Genentech, A Member of the Roche Group, South San Francisco, CA, USA
| | - Steffen Lippold
- Protein Analytical Chemistry, Genentech, A Member of the Roche Group, South San Francisco, CA, USA
| | - John Stobaugh
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA
| | - Christian Schöneich
- Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA
| | - Feng Yang
- Protein Analytical Chemistry, Genentech, A Member of the Roche Group, South San Francisco, CA, USA
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Vaz-Rodrigues R, Mazuecos L, Villar M, Contreras M, Artigas-Jerónimo S, González-García A, Gortázar C, de la Fuente J. Multi-omics analysis of zebrafish response to tick saliva reveals biological processes associated with alpha-Gal syndrome. Biomed Pharmacother 2023; 168:115829. [PMID: 37922649 DOI: 10.1016/j.biopha.2023.115829] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/17/2023] [Accepted: 10/31/2023] [Indexed: 11/07/2023] Open
Abstract
The alpha-Gal syndrome (AGS) is a tick-borne allergy. A multi-omics approach was used to determine the effect of tick saliva and mammalian meat consumption on zebrafish gut transcriptome and proteome. Bioinformatics analysis using R software was focused on significant biological and metabolic pathway changes associated with AGS. Ortholog mapping identified highly concordant human ortholog genes for the detection of disease-enriched pathways. Tick saliva treatment increased zebrafish mortality, incidence of hemorrhagic type allergic reactions and changes in behavior and feeding patterns. Transcriptomics analysis showed downregulation of biological and metabolic pathways correlated with anti-alpha-Gal IgE and allergic reactions to tick saliva affecting blood circulation, cardiac and vascular smooth muscle contraction, behavior and sensory perception. Disease enrichment analysis revealed downregulated orthologous genes associated with human disorders affecting nervous, musculoskeletal, and cardiovascular systems. Proteomics analysis revealed suppression of pathways associated with immune system production of reactive oxygen species and cardiac muscle contraction. Underrepresented proteins were mainly linked to nervous and metabolic human disorders. Multi-omics data revealed inhibition of pathways associated with adrenergic signaling in cardiomyocytes, and heart and muscle contraction. Results identify tick saliva-related biological pathways supporting multisystemic organ involvement and linking α-Gal sensitization with other illnesses for the identification of potential disease biomarkers.
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Affiliation(s)
- Rita Vaz-Rodrigues
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
| | - Lorena Mazuecos
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
| | - Margarita Villar
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain; Biochemistry Section, Faculty of Science and Chemical Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
| | - Marinela Contreras
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
| | - Sara Artigas-Jerónimo
- Biochemistry Section, Faculty of Science and Chemical Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
| | - Almudena González-García
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
| | - Christian Gortázar
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
| | - José de la Fuente
- SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain; Department of Veterinary Pathobiology, Centre for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
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12
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Ünal D, Eyice-Karabacak D, Kutlu A, Demir S, Tüzer C, Arslan AF, Işık SR, Gelincik A. Oral immunotherapy in alpha-gal red meat allergy: Could specific IgE be a potential biomarker in monitoring management? Allergy 2023; 78:3241-3251. [PMID: 37545316 DOI: 10.1111/all.15840] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 06/21/2023] [Accepted: 07/05/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND Oral immunotherapy (OIT) is a promising treatment for food allergies. Our aim was to establish the long-term safety and efficacy of a novel red meat (RM) OIT in galactose-alpha-1,3-galactose (alpha-gal) allergy in adults. METHODS Out of 20 patients with confirmed RM allergy, five (41.66%) underwent an early OIT, seven (58.33%) underwent a delayed protocol and eight patients who were not desensitized formed the patient control group. 15 and 27 day RM OIT for early-onset and delayed-onset alpha-gal allergy were administered, respectively. Desensitized patients were recommended to continue eating at least 100 g RM every day for 6 months and every other day in the following 6 months. After a year, the consumption was recommended 2/3 times in a week. Patients were followed up with skin tests with commercial beef and lamb extracts, fresh raw/cooked beef and lamb and cetuximab and also with serum alpha-gal specific Immunoglobulin-E (sIgE) in the first and fifth years. RESULTS All patients who underwent OIT became tolerant to RM. During the 5 year follow-up, the median alpha-gal sIgE concentration gradually decreased in nine patients who consumed RM uneventfully while remained unchanged in the control group (p = .016). In two patients, rare tick bites acted as inducers of hypersensitivity reactions with concomitant elevation of alpha-gal sIgE concentrations whereas one patient with low follow-up alpha-gal sIgE concentrations consumed RM uneventfully after frequent tick bites. CONCLUSIONS Our study showed the long-term safety and efficacy of alpha-gal OIT. Additionally, alpha-gal sIgE seems to be a potential biomarker to monitor OIT.
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Affiliation(s)
- D Ünal
- Division of Immunology and Allergy Diseases, Internal Medicine Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - D Eyice-Karabacak
- Division of Immunology and Allergy Diseases, Internal Medicine Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - A Kutlu
- Medical Park Hospital Ordu, Ordu, Turkey
| | - S Demir
- Division of Immunology and Allergy Diseases, Internal Medicine Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - C Tüzer
- Division of Immunology and Allergy Diseases, Internal Medicine Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - A F Arslan
- Division of Immunology and Allergy Diseases, Internal Medicine Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - S R Işık
- Division of Immunology and Allergy Diseases, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey
| | - A Gelincik
- Division of Immunology and Allergy Diseases, Internal Medicine Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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13
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Sharma SR, Choudhary SK, Vorobiov J, Commins SP, Karim S. Tick bite-induced Alpha-Gal Syndrome and Immunologic Responses in an Alpha-Gal Deficient Murine Model. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.11.09.566281. [PMID: 38014105 PMCID: PMC10680608 DOI: 10.1101/2023.11.09.566281] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
Introduction Alpha-Gal Syndrome (AGS) is a delayed allergic reaction due to specific IgE antibodies targeting galactose-α-1,3-galactose (α-gal), a carbohydrate found in red meat. This condition has gained significant attention globally due to its increasing prevalence, with more than 450,000 cases estimated in the United States alone. Previous research has established a connection between AGS and tick bites, which sensitize individuals to α-gal antigens and elevate the levels of α-gal specific IgE. However, the precise mechanism by which tick bites influence the hosťs immune system and contribute to the development of AGS remains poorly understood. This study investigates various factors related to ticks and the host associated with the development of AGS following a tick bite, using mice with a targeted disruption of alpha-1,3-galactosyltransferase (AGKO) as a model organism. Methods Lone-star tick (Amblyomma americanum) and gulf-coast tick (Amblyomma maculatum) nymphs were used to sensitize AGKO mice, followed by pork meat challenge. Tick bite site biopsies from sensitized and non-sensitized mice were subjected to mRNA gene expression analysis to assess the host immune response. Antibody responses in sensitized mice were also determined. Results Our results showed a significant increase in the titer of total IgE, IgG1, and α-gal IgG1 antibodies in the lone-star tick-sensitized AGKO mice compared to the gulf-coast tick-sensitized mice. Pork challenge in Am. americanum -sensitized mice led to a decline in body temperature after the meat challenge. Gene expression analysis revealed that Am. americanum bites direct mouse immunity toward Th2 and facilitate host sensitization to the α-gal antigen, while Am. maculatum did not. Conclusion This study supports the hypothesis that specific tick species may increase the risk of developing α-gal-specific IgE and hypersensitivity reactions or AGS, thereby providing opportunities for future research on the mechanistic role of tick and host-related factors in AGS development.
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Affiliation(s)
- Surendra Raj Sharma
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
| | - Shailesh K Choudhary
- Department of Medicine & Pediatrics, University of North Carolina, Chapel Hill, NC 27599-7280, USA
| | - Julia Vorobiov
- Department of Medicine & Pediatrics, University of North Carolina, Chapel Hill, NC 27599-7280, USA
| | - Scott P Commins
- Department of Medicine & Pediatrics, University of North Carolina, Chapel Hill, NC 27599-7280, USA
| | - Shahid Karim
- School of Biological, Environment and Earth Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA
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Wu H, Chen B, Wu Y, Gao J, Li X, Tong P, Wu Y, Meng X, Chen H. New Perspectives on Food Matrix Modulation of Food Allergies: Immunomodulation and Component Interactions. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:13181-13196. [PMID: 37646334 DOI: 10.1021/acs.jafc.3c03192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Food allergy is a multifactorial interplay process influenced not only by the structure and function of the allergen itself but also by other components of the food matrix. For food, before it is thoroughly digested and absorbed, numerous factors make the food matrix constantly change. This will also lead to changes in the chemistry, biochemical composition, and structure of the various components in the matrix, resulting in multifaceted effects on food allergies. In this review, we reveal the relationship between the food matrix and food allergies and outline the immune role of the components in the food matrix, while highlighting the ways and pathways in which the components in the food matrix interact and their impact on food allergies. The in-depth study of the food matrix will essentially explore the mechanism of food allergies and bring about new ideas and breakthroughs for the prevention and treatment of food allergies.
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Affiliation(s)
- Huan Wu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- College of Food Science and Technology, Nanchang University, Nanchang 330031, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Bihua Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- College of Food Science and Technology, Nanchang University, Nanchang 330031, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Yuhong Wu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- College of Food Science and Technology, Nanchang University, Nanchang 330031, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Jinyan Gao
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- College of Food Science and Technology, Nanchang University, Nanchang 330031, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Xin Li
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- College of Food Science and Technology, Nanchang University, Nanchang 330031, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Ping Tong
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Yong Wu
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Xuanyi Meng
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Hongbing Chen
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, People's Republic of China
- Sino-German Joint Research Institute, Nanchang University, Nanchang 330047, People's Republic of China
- Jiangxi Province Key Laboratory of Food Allergy, Nanchang University, Nanchang, 330047, People's Republic of China
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15
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Lewies A, Botes L, van den Heever JJ, Dohmen PM, Smit FE. Monomeric glutaraldehyde fixation and amino acid detoxification of decellularized bovine pericardium for production of biocompatible tissue with tissue-guided regenerative potential. Heliyon 2023; 9:e19712. [PMID: 37809671 PMCID: PMC10559009 DOI: 10.1016/j.heliyon.2023.e19712] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 08/23/2023] [Accepted: 08/30/2023] [Indexed: 10/10/2023] Open
Abstract
The effect of monomeric glutaraldehyde fixation and amino acid detoxification on biocompatibility and tissue-guided regenerative potential of decellularized bovine pericardium was evaluated. The degree of cross-linking, porosity, enzymatic degradation, alpha-galactosyl content, the efficacy of detoxification, and cytotoxicity towards human epithelial cells were assessed. Tissue was subcutaneously implanted for eight weeks in male juvenile Sprague-Dawley rats, and mechanical properties, host cell infiltration, and calcification were evaluated. Three groups were compared i) decellularized tissue, ii) decellularized, monomeric glutaraldehyde fixed and amino acid detoxified tissue, and iii) commercial glutaraldehyde fixed non-decellularized tissue (Glycar®) (n = 6 rats per group). The fixation process gave a high degree of cross-linking (>85%), and was resistant to enzymatic degradation, with no significant effect on porosity. The detoxification process was effective, and the tissue was not toxic to mammalian cells in vitro. Tissue from both decellularized groups had significantly higher (p < 0.05) porosity and host cell infiltration in vivo. The process mitigated calcification. A non-significant decrease in the alpha-galactosyl content was observed, which increased when including the alpha-galactosidase enzyme. Mechanical properties were maintained. The fixation and detoxification process adequately removes free aldehyde groups and reduces toxicity, preventing enzymatic degradation and allowing for host cell infiltration while mitigating calcification and retaining the mechanical properties of the tissue. This process can be considered for processing decellularized bovine pericardium with tissue-guided regeneration potential for use in cardiovascular bioprostheses; however, methods of further reducing antigenicity, such as the use of enzymes, should be investigated.
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Affiliation(s)
- Angélique Lewies
- Department of Cardiothoracic Surgery, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
| | - Lezelle Botes
- Department of Health Sciences, Central University of Technology, Free State, Bloemfontein, South Africa
| | | | - Pascal Maria Dohmen
- Department of Cardiothoracic Surgery, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
- Department of Cardiac Surgery, Heart Centre Rostock, University of Rostock, Germany
| | - Francis Edwin Smit
- Department of Cardiothoracic Surgery, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa
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16
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Benders-Guedj M, Köberle M, Hofmann H, Biedermann T, Darsow U. High-risk groups for alpha-gal sensitization. Allergol Select 2023; 7:140-148. [PMID: 37705677 PMCID: PMC10495941 DOI: 10.5414/alx02424e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 06/27/2023] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND Tick bite-induced IgE-mediated reactions to the oligosaccharide galactose α-1,3-galactose (alpha-gal) are increasingly recognized. This study investigated alpha-gal sensitization in three groups with different tick bite exposure. MATERIALS AND METHODS Specific IgE antibodies to alpha-gal and total IgE were investigated in 485 patients with Lyme borreliosis with different disease manifestations and compared to a control group of 200 randomly selected patients without increased exposure to tick bites. A group of 232 hunters and forest workers served as a model for multiple tick bites. RESULTS Specific IgE (sIgE) antibodies to alpha-gal (> 0.1 kU/L) were found in 12.6% of all borreliosis samples compared to the control group with 9% (relative risk 1.4; 95% CI 0.85 - 2.3; not significant (n.s.). The highest prevalence of sIgE to alpha-gal was observed in hunters and forest service employees (22.8%, relative risk 2.5; 95% CI 1.5 - 4.2; p < 0.001). Higher age and elevated total IgE were also associated with alpha-gal sensitization. CONCLUSION IgE sensitization to alpha-gal tends to be more frequent in tick-exposed patients with borreliosis than in controls (n.s.). Moreover, hunters and forest workers show an even higher rate of elevated IgE to alpha-gal. Thus, frequent tick contact may result in alpha-gal sensitization. In the area of Munich, the prevalence of alpha-gal sensitization appears lower than in the state of Baden-Württemberg and lower than in the USA, which may be due to the difference in tick species or the frequency of tick exposure. This study could show that alpha-gal sensitization and presumably alpha-gal syndrome does not seem to be a modern problem but existed already more than 30 years ago.
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Affiliation(s)
- Marie Benders-Guedj
- Department of Dermatology and Allergy Biederstein, Faculty of Medicine, Technical University of Munich, Munich, Germany
| | - Martin Köberle
- Department of Dermatology and Allergy Biederstein, Faculty of Medicine, Technical University of Munich, Munich, Germany
| | - Heidelore Hofmann
- Department of Dermatology and Allergy Biederstein, Faculty of Medicine, Technical University of Munich, Munich, Germany
| | - Tilo Biedermann
- Department of Dermatology and Allergy Biederstein, Faculty of Medicine, Technical University of Munich, Munich, Germany
| | - Ulf Darsow
- Department of Dermatology and Allergy Biederstein, Faculty of Medicine, Technical University of Munich, Munich, Germany
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17
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Popova J, Bets V, Kozhevnikova E. Perspectives in Genome-Editing Techniques for Livestock. Animals (Basel) 2023; 13:2580. [PMID: 37627370 PMCID: PMC10452040 DOI: 10.3390/ani13162580] [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: 07/07/2023] [Revised: 08/08/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
Genome editing of farm animals has undeniable practical applications. It helps to improve production traits, enhances the economic value of livestock, and increases disease resistance. Gene-modified animals are also used for biomedical research and drug production and demonstrate the potential to be used as xenograft donors for humans. The recent discovery of site-specific nucleases that allow precision genome editing of a single-cell embryo (or embryonic stem cells) and the development of new embryological delivery manipulations have revolutionized the transgenesis field. These relatively new approaches have already proven to be efficient and reliable for genome engineering and have wide potential for use in agriculture. A number of advanced methodologies have been tested in laboratory models and might be considered for application in livestock animals. At the same time, these methods must meet the requirements of safety, efficiency and availability of their application for a wide range of farm animals. This review aims at covering a brief history of livestock animal genome engineering and outlines possible future directions to design optimal and cost-effective tools for transgenesis in farm species.
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Affiliation(s)
- Julia Popova
- Laboratory of Bioengineering, Novosibirsk State Agrarian University, 630039 Novosibirsk, Russia; (J.P.); (V.B.)
| | - Victoria Bets
- Laboratory of Bioengineering, Novosibirsk State Agrarian University, 630039 Novosibirsk, Russia; (J.P.); (V.B.)
- Center of Technological Excellence, Novosibirsk State Technical University, 630073 Novosibirsk, Russia
| | - Elena Kozhevnikova
- Laboratory of Bioengineering, Novosibirsk State Agrarian University, 630039 Novosibirsk, Russia; (J.P.); (V.B.)
- Laboratory of Experimental Models of Cognitive and Emotional Disorders, Scientific-Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia
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18
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Dramburg S, Hilger C, Santos AF, de Las Vecillas L, Aalberse RC, Acevedo N, Aglas L, Altmann F, Arruda KL, Asero R, Ballmer-Weber B, Barber D, Beyer K, Biedermann T, Bilo MB, Blank S, Bosshard PP, Breiteneder H, Brough HA, Bublin M, Campbell D, Caraballo L, Caubet JC, Celi G, Chapman MD, Chruszcz M, Custovic A, Czolk R, Davies J, Douladiris N, Eberlein B, Ebisawa M, Ehlers A, Eigenmann P, Gadermaier G, Giovannini M, Gomez F, Grohman R, Guillet C, Hafner C, Hamilton RG, Hauser M, Hawranek T, Hoffmann HJ, Holzhauser T, Iizuka T, Jacquet A, Jakob T, Janssen-Weets B, Jappe U, Jutel M, Kalic T, Kamath S, Kespohl S, Kleine-Tebbe J, Knol E, Knulst A, Konradsen JR, Korošec P, Kuehn A, Lack G, Le TM, Lopata A, Luengo O, Mäkelä M, Marra AM, Mills C, Morisset M, Muraro A, Nowak-Wegrzyn A, Nugraha R, Ollert M, Palosuo K, Pastorello EA, Patil SU, Platts-Mills T, Pomés A, Poncet P, Potapova E, Poulsen LK, Radauer C, Radulovic S, Raulf M, Rougé P, Sastre J, Sato S, Scala E, Schmid JM, Schmid-Grendelmeier P, Schrama D, Sénéchal H, Traidl-Hoffmann C, Valverde-Monge M, van Hage M, van Ree R, Verhoeckx K, Vieths S, Wickman M, Zakzuk J, Matricardi PM, et alDramburg S, Hilger C, Santos AF, de Las Vecillas L, Aalberse RC, Acevedo N, Aglas L, Altmann F, Arruda KL, Asero R, Ballmer-Weber B, Barber D, Beyer K, Biedermann T, Bilo MB, Blank S, Bosshard PP, Breiteneder H, Brough HA, Bublin M, Campbell D, Caraballo L, Caubet JC, Celi G, Chapman MD, Chruszcz M, Custovic A, Czolk R, Davies J, Douladiris N, Eberlein B, Ebisawa M, Ehlers A, Eigenmann P, Gadermaier G, Giovannini M, Gomez F, Grohman R, Guillet C, Hafner C, Hamilton RG, Hauser M, Hawranek T, Hoffmann HJ, Holzhauser T, Iizuka T, Jacquet A, Jakob T, Janssen-Weets B, Jappe U, Jutel M, Kalic T, Kamath S, Kespohl S, Kleine-Tebbe J, Knol E, Knulst A, Konradsen JR, Korošec P, Kuehn A, Lack G, Le TM, Lopata A, Luengo O, Mäkelä M, Marra AM, Mills C, Morisset M, Muraro A, Nowak-Wegrzyn A, Nugraha R, Ollert M, Palosuo K, Pastorello EA, Patil SU, Platts-Mills T, Pomés A, Poncet P, Potapova E, Poulsen LK, Radauer C, Radulovic S, Raulf M, Rougé P, Sastre J, Sato S, Scala E, Schmid JM, Schmid-Grendelmeier P, Schrama D, Sénéchal H, Traidl-Hoffmann C, Valverde-Monge M, van Hage M, van Ree R, Verhoeckx K, Vieths S, Wickman M, Zakzuk J, Matricardi PM, Hoffmann-Sommergruber K. EAACI Molecular Allergology User's Guide 2.0. Pediatr Allergy Immunol 2023; 34 Suppl 28:e13854. [PMID: 37186333 DOI: 10.1111/pai.13854] [Show More Authors] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 09/05/2022] [Indexed: 05/17/2023]
Abstract
Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.
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Affiliation(s)
- Stephanie Dramburg
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Christiane Hilger
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - 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 London, Guy's and St Thomas' Hospital, London, United Kingdom
| | | | - Rob C Aalberse
- Sanquin Research, Dept Immunopathology, University of Amsterdam, Amsterdam, The Netherlands
- Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Nathalie Acevedo
- Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia, Colombia
| | - Lorenz Aglas
- Department of Biosciences and Medical Biology, Paris Lodron University Salzburg, Salzburg, Austria
| | - Friedrich Altmann
- Department of Chemistry, University of Natural Resources and Life Sciences, Vienna, Austria
| | - Karla L Arruda
- Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Sao Paulo, Brasil, Brazil
| | - Riccardo Asero
- Ambulatorio di Allergologia, Clinica San Carlo, Paderno Dugnano, Italy
| | - Barbara Ballmer-Weber
- Klinik für Dermatologie und Allergologie, Kantonsspital St. Gallen, St. Gallen, Switzerland
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Domingo Barber
- Institute of Applied Molecular Medicine Nemesio Diez (IMMAND), Department of Basic Medical Sciences, Facultad de Medicina, Universidad San Pablo CEU, CEU Universities, Madrid, Spain
- RETIC ARADyAL and RICORS Enfermedades Inflamatorias (REI), Madrid, Spain
| | - Kirsten Beyer
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Tilo Biedermann
- Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University Munich, Munich, Germany
| | - Maria Beatrice Bilo
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
- Allergy Unit Department of Internal Medicine, University Hospital Ospedali Riuniti di Ancona, Torrette, Italy
| | - Simon Blank
- Center of Allergy and Environment (ZAUM), Technical University of Munich, School of Medicine and Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany
| | - Philipp P Bosshard
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
| | - Heimo Breiteneder
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Helen A Brough
- 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
- Children's Allergy Service, Evelina London, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Merima Bublin
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Dianne Campbell
- Department of Allergy and Immunology, Children's Hospital at Westmead, Sydney Children's Hospitals Network, Sydney, New South Wales, Australia
- Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
| | - Luis Caraballo
- Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia, Colombia
| | - Jean Christoph Caubet
- Pediatric Allergy Unit, Department of Child and Adolescent, University Hospitals of Geneva, Geneva, Switzerland
| | - Giorgio Celi
- Centro DH Allergologia e Immunologia Clinica ASST- MANTOVA (MN), Mantova, Italy
| | | | - Maksymilian Chruszcz
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA
| | - Adnan Custovic
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Rebecca Czolk
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
- Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Janet Davies
- Queensland University of Technology, Centre for Immunology and Infection Control, School of Biomedical Sciences, Herston, Queensland, Australia
- Metro North Hospital and Health Service, Emergency Operations Centre, Herston, Queensland, Australia
| | - Nikolaos Douladiris
- Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Bernadette Eberlein
- Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University Munich, Munich, Germany
| | - Motohiro Ebisawa
- Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan
| | - Anna Ehlers
- Chemical Biology and Drug Discovery, Utrecht University, Utrecht, The Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Philippe Eigenmann
- Pediatric Allergy Unit, Department of Child and Adolescent, University Hospitals of Geneva, Geneva, Switzerland
| | - Gabriele Gadermaier
- Department of Biosciences and Medical Biology, Paris Lodron University Salzburg, Salzburg, Austria
| | - Mattia Giovannini
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Francisca Gomez
- Allergy Unit IBIMA-Hospital Regional Universitario de Malaga, Malaga, Spain
- Spanish Network for Allergy research RETIC ARADyAL, Malaga, Spain
| | - Rebecca Grohman
- NYU Langone Health, Department of Internal Medicine, New York, New York, USA
| | - Carole Guillet
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Christine Hafner
- Department of Dermatology, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria
| | - Robert G Hamilton
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Michael Hauser
- Department of Biosciences and Medical Biology, Paris Lodron University Salzburg, Salzburg, Austria
| | - Thomas Hawranek
- Department of Dermatology and Allergology, Paracelsus Private Medical University, Salzburg, Austria
| | - Hans Jürgen Hoffmann
- Institute for Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | | | - Tomona Iizuka
- Laboratory of Protein Science, Graduate School of Life Science, Hokkaido University, Sapporo, Japan
| | - Alain Jacquet
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Thilo Jakob
- Department of Dermatology and Allergology, University Medical Center, Justus Liebig University Gießen, Gießen, Germany
| | - Bente Janssen-Weets
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
- Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark
| | - Uta Jappe
- Division of Clinical and Molecular Allergology, Priority Research Area Asthma and Allergy, Research Center Borstel, Borstel, Germany
- Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research, Germany
- Interdisciplinary Allergy Outpatient Clinic, Dept. of Pneumology, University of Lübeck, Lübeck, Germany
| | - Marek Jutel
- Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland
| | - Tanja Kalic
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
- Department of Dermatology, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria
| | - Sandip Kamath
- Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
- Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
| | - Sabine Kespohl
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr- Universität Bochum, Bochum, Germany
| | - Jörg Kleine-Tebbe
- Allergy & Asthma Center Westend, Outpatient Clinic and Clinical Research Center, Berlin, Germany
| | - Edward Knol
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - André Knulst
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Jon R Konradsen
- Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
- Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
| | - Peter Korošec
- University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| | - Annette Kuehn
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Gideon Lack
- 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 London, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Thuy-My Le
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Andreas Lopata
- Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
- Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
| | - Olga Luengo
- RETIC ARADyAL and RICORS Enfermedades Inflamatorias (REI), Madrid, Spain
- Allergy Section, Internal Medicine Department, Vall d'Hebron University Hospital, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Mika Mäkelä
- Division of Allergy, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- Pediatric Department, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
| | | | - Clare Mills
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK
| | | | - Antonella Muraro
- Food Allergy Referral Centre, Department of Woman and Child Health, Padua University Hospital, Padua, Italy
| | - Anna Nowak-Wegrzyn
- Division of Pediatric Allergy and Immunology, NYU Grossman School of Medicine, Hassenfeld Children's Hospital, New York, New York, USA
- Department of Pediatrics, Gastroenterology and Nutrition, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
| | - Roni Nugraha
- Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
- Department of Aquatic Product Technology, Faculty of Fisheries and Marine Science, IPB University, Bogor, Indonesia
| | - Markus Ollert
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
- Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark
| | - Kati Palosuo
- Department of Allergology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
| | | | - Sarita Ulhas Patil
- Division of Rheumatology, Allergy and Immunology, Departments of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Division of Allergy and Immunology, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Thomas Platts-Mills
- Division of Allergy and Clinical Immunology, University of Virginia, Charlottesville, Virginia, USA
| | | | - Pascal Poncet
- Institut Pasteur, Immunology Department, Paris, France
- Allergy & Environment Research Team Armand Trousseau Children Hospital, APHP, Paris, France
| | - Ekaterina Potapova
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Lars K Poulsen
- Allergy Clinic, Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark
| | - Christian Radauer
- Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
| | - Suzana Radulovic
- 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
- Children's Allergy Service, Evelina London, Guy's and St Thomas' Hospital, London, United Kingdom
| | - Monika Raulf
- Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr- Universität Bochum, Bochum, Germany
| | - Pierre Rougé
- UMR 152 PharmaDev, IRD, Université Paul Sabatier, Faculté de Pharmacie, Toulouse, France
| | - Joaquin Sastre
- Allergy Service, Fundación Jiménez Díaz; CIBER de Enfermedades Respiratorias (CIBERES); Faculty of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
| | - Sakura Sato
- Allergy Department, 2nd Paediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Enrico Scala
- Clinical and Laboratory Molecular Allergy Unit - IDI- IRCCS, Fondazione L M Monti Rome, Rome, Italy
| | - Johannes M Schmid
- Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Peter Schmid-Grendelmeier
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
- Christine Kühne Center for Allergy Research and Education CK-CARE, Davos, Switzerland
| | - Denise Schrama
- Centre of Marine Sciences (CCMAR), Universidade do Algarve, Faro, Portugal
| | - Hélène Sénéchal
- Allergy & Environment Research Team Armand Trousseau Children Hospital, APHP, Paris, France
| | - Claudia Traidl-Hoffmann
- Christine Kühne Center for Allergy Research and Education CK-CARE, Davos, Switzerland
- Department of Environmental Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany
| | - Marcela Valverde-Monge
- Allergy Service, Fundación Jiménez Díaz; CIBER de Enfermedades Respiratorias (CIBERES); Faculty of Medicine, Universidad Autonoma de Madrid, Madrid, Spain
| | - Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Ronald van Ree
- Department of Experimental Immunology and Department of Otorhinolaryngology, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Kitty Verhoeckx
- Department of Immunology and Dermatology/ Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Stefan Vieths
- Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany
| | - Magnus Wickman
- Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Josefina Zakzuk
- Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia, Colombia
| | - Paolo M Matricardi
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
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Lis K, Ukleja-Sokołowska N, Karwowska K, Wernik J, Pawłowska M, Bartuzi Z. The Two-Sided Experimental Model of ImmunoCAP Inhibition Test as a Useful Tool for the Examination of Allergens Cross-Reactivity on the Example of α-Gal and Mammalian Meat Sensitization-A Preliminary Study. Curr Issues Mol Biol 2023; 45:1168-1182. [PMID: 36826022 PMCID: PMC9955645 DOI: 10.3390/cimb45020077] [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: 12/23/2022] [Revised: 01/25/2023] [Accepted: 01/30/2023] [Indexed: 02/04/2023] Open
Abstract
Cross-reactivity of allergens is the cause of various, sometimes unexpected, clinical reactions. There are no standard methods to investigate cross-reactivity. We present an experimental model of a two-sided inhibition test (IT) on ImmunoCAP membranes (CAP). We constructed the described model based on the known cross-allergy syndrome to red meat developing in people bitten by ticks (α-Gal syndrome; AGS). Some individuals who are bitten by ticks develop IgE antibodies specific to the carbohydrate determinant, galactose-α-1,3-galactose (α-Gal), present in the tick's saliva. These antibodies can cross-react with α-Gal molecules expressed on mammalian meat proteins. The well-known property of anti-α-Gal IgE antibodies binding by various sources of this allergen was used by us in the proposed model of the two-sided inhibition test on ImmunoCAP membranes. We expected that anti-α-Gal IgE antibodies bind allergens from mammalian meat and blocking them abolishes this reactivity, and the two-sided inhibition test model we proposed on ImmunoCAP membranes allowed us to observe such a relationship. We conducted the experiment three times on biological material from people with different clinical manifestations of allergy to α-Gal, each time obtaining similar results. In conclusion, the model of bilateral inhibition on ImmunoCAP membranes proposed by us seems to be an attractive, simple tool for direct testing of allergic cross-reactivity.
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Affiliation(s)
- Kinga Lis
- Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Ujejskiego 75, 85168 Bydgoszcz, Poland
- Correspondence:
| | - Natalia Ukleja-Sokołowska
- Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Ujejskiego 75, 85168 Bydgoszcz, Poland
| | - Kornelia Karwowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Świętego Floriana 12, 85030 Bydgoszcz, Poland
| | - Joanna Wernik
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Świętego Floriana 12, 85030 Bydgoszcz, Poland
| | - Małgorzata Pawłowska
- Department of Infectious Diseases and Hepatology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Świętego Floriana 12, 85030 Bydgoszcz, Poland
| | - Zbigniew Bartuzi
- Department of Allergology, Clinical Immunology and Internal Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, ul. Ujejskiego 75, 85168 Bydgoszcz, Poland
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Tai A, Landao-Bassonga E, Chen Z, Tran M, Allan B, Ruan R, Calder D, Goonewardene M, Ngo H, Zheng MH. Systematic evaluation of three porcine-derived collagen membranes for guided bone regeneration. BIOMATERIALS TRANSLATIONAL 2023; 4:41-50. [PMID: 37206304 PMCID: PMC10189808 DOI: 10.12336/biomatertransl.2023.01.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 02/22/2023] [Accepted: 03/02/2023] [Indexed: 05/21/2023]
Abstract
Guided bone regeneration is one of the most common surgical treatment modalities performed when an additional alveolar bone is required to stabilize dental implants in partially and fully edentulous patients. The addition of a barrier membrane prevents non-osteogenic tissue invasion into the bone cavity, which is key to the success of guided bone regeneration. Barrier membranes can be broadly classified as non-resorbable or resorbable. In contrast to non-resorbable membranes, resorbable barrier membranes do not require a second surgical procedure for membrane removal. Commercially available resorbable barrier membranes are either synthetically manufactured or derived from xenogeneic collagen. Although collagen barrier membranes have become increasingly popular amongst clinicians, largely due to their superior handling qualities compared to other commercially available barrier membranes, there have been no studies to date that have compared commercially available porcine-derived collagen membranes with respect to surface topography, collagen fibril structure, physical barrier property, and immunogenic composition. This study evaluated three commercially available non-crosslinked porcine-derived collagen membranes (Striate+TM, Bio-Gide® and CreosTM Xenoprotect). Scanning electron microscopy revealed similar collagen fibril distribution on both the rough and smooth sides of the membranes as well as the similar diameters of collagen fibrils. However, D-periodicity of the fibrillar collagen is significantly different among the membranes, with Striate+TM membrane having the closest D-periodicity to native collagen I. This suggests that there is less deformation of collagen during manufacturing process. All collagen membranes showed superior barrier property evidenced by blocking 0.2-16.4 μm beads passing through the membranes. To examine the immunogenic agents in these membranes, we examined the membranes for the presence of DNA and alpha-gal by immunohistochemistry. No alpha-gal or DNA was detected in any membranes. However, using a more sensitive detection method (real-time polymerase chain reaction), a relatively strong DNA signal was detected in Bio-Gide® membrane, but not Striate+TM and CreosTM Xenoprotect membranes. Our study concluded that these membranes are similar but not identical, probably due to the different ages and sources of porcine tissues, as well as different manufacturing processes. We recommend further studies to understand the clinical implications of these findings.
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Affiliation(s)
- Andrew Tai
- Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
- Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia
| | - Euphemie Landao-Bassonga
- Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
- Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia
| | - Ziming Chen
- Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Minh Tran
- UWA Dental School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Brent Allan
- Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
- UWA Dental School, The University of Western Australia, Nedlands, Western Australia, Australia
- Oral and Maxillofacial Department, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia
| | - Rui Ruan
- Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Dax Calder
- UWA Dental School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Mithran Goonewardene
- UWA Dental School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Hien Ngo
- UWA Dental School, The University of Western Australia, Nedlands, Western Australia, Australia
| | - Ming Hao Zheng
- Centre for Orthopaedic Research, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Western Australia, Australia
- Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia
- Corresponding authors: Ming Hao Zheng,
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21
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Poziomkowska-Gęsicka I. Idiopathic Anaphylaxis? Analysis of Data from the Anaphylaxis Registry for West Pomerania Province, Poland. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:16716. [PMID: 36554595 PMCID: PMC9779638 DOI: 10.3390/ijerph192416716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 12/05/2022] [Accepted: 12/07/2022] [Indexed: 06/17/2023]
Abstract
The most common causes of anaphylaxis, according to various authors and depending on the age of the studied groups, are: Hymenoptera venom, food, and medications. Unfortunately, we are not always able to indicate the cause of anaphylaxis. There are data in the literature where as many as 41% of all cases are idiopathic anaphylaxis. Since the introduction of new diagnostic methods such as molecular diagnostics (MD) in our centre, the percentage of idiopathic anaphylaxis in the Anaphylaxis Register has significantly decreased. The purpose of this study was to identify possible causes of idiopathic anaphylaxis in patients with a history of moderate to severe anaphylactic reactions. After using MD, the causative agent was found in another 29 people. The proportion of people with idiopathic anaphylaxis in the Registry decreased from 9.2% to 3.5%. There were no significant differences in the incidence, although men appear to be slightly more common in primary idiopathic anaphylaxis. The mean age of primary idiopathic anaphylaxis was 40 years, but this was as high as 51 for anaphylaxis with alpha-gal allergy. Exercise may or may not be present as a cofactor despite its established role, e.g., in wheat-dependent exercise-induced anaphylaxis (WDEIA). In most of the analyzed cases, i.e., 70%, the reaction took place within an hour. The longest time interval from exposure to the development of symptoms is in the case of alpha-gal allergy; in this analysis, it was at least 5 h after ingestion of the so-called "red meat". Patients are not aware of the disease, or further attacks cannot be prevented. As many as 80% had idiopathic anaphylaxis prior to visiting the centre, and 80% developed anaphylaxis after visiting the centre, which emphasizes the need to not stop the medical team in their search for the causes. As many as 93% of cases required medical intervention, of which adrenaline was used only in 34.5%, antihistamines in 86%, systemic glucocorticosteroids (sCS) in 75%, and fluids in 62% of cases. A total of 83% of patients received an emergency kit for self-administration. Idiopathic anaphylaxis can be resolved as known-cause anaphylaxis after a thorough medical history and, if possible, without exposing the patient after using appropriate, modern in vitro diagnostic methods, including molecular diagnostics. The diagnosis of idiopathic anaphylaxis should extend the diagnosis to include alpha-gal syndrome, LTP syndrome and WDEIA.
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Affiliation(s)
- Iwona Poziomkowska-Gęsicka
- Clinical Allergology Department, Pomeranian Medical University (PMU) in Szczecin, 70-111 Szczecin, Poland
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22
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Vaz-Rodrigues R, Mazuecos L, de la Fuente J. Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS). J Asthma Allergy 2022; 15:957-970. [PMID: 35879928 PMCID: PMC9307871 DOI: 10.2147/jaa.s265660] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 07/12/2022] [Indexed: 11/23/2022] Open
Abstract
The α-Gal syndrome (AGS) is a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in foods containing the oligosaccharide galactose-α-1,3-galactose (α-Gal) such as mammalian meat or dairy products. Clinical presentation of AGS can also comprise immediate hypersensitivity due to anticancer therapy, gelatin-containing vaccines or mammalian serum-based antivenom. The IgE initial sensitization is caused by hard-bodied tick bites and symptomatic individuals typically develop delayed pruritus, urticaria, angioedema, anaphylaxis, malaise or gut-related symptoms. Due to inapparent presentation, delayed reactions and a wide variety of patients´ clinical history, the AGS diagnosis and treatment remain challenging. This review covers not only current diagnostic methods used for AGS such as the skin prick test (SPT), the oral food challenge (OFC), anti-α-Gal IgE levels measurement and the basophil activation test (BAT), but also potentially relevant next-generation diagnostic tools like the mast cell activation test (MAT), the histamine-release (HR) assay, omics technologies and model-based reasoning (MBR). Moreover, it focuses on the therapeutical medical and non-medical methods available and current research methods that are being applied in order to elucidate the molecular, physiological and immune mechanisms underlying this allergic disorder. Lastly, future treatment and preventive tools are also discussed, being of utmost importance for the identification of tick salivary molecules, with or without α-Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development. Bearing in mind climate change, the tick-host paradigm will shift towards an increasing number of AGS cases in new regions worldwide, which will pose new challenges for clinicians in the future.
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Affiliation(s)
- Rita Vaz-Rodrigues
- SaBio (Health and Biotechnology), Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ciudad Real, 13005, Spain
| | - Lorena Mazuecos
- SaBio (Health and Biotechnology), Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ciudad Real, 13005, Spain
| | - José de la Fuente
- SaBio (Health and Biotechnology), Instituto de Investigación en Recursos Cinegéticos IREC (CSIC-UCLM-JCCM), Ciudad Real, 13005, Spain.,Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, 74078, USA
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23
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Chakrapani N, Fischer J, Swiontek K, Codreanu-Morel F, Hannachi F, Morisset M, Mugemana C, Bulaev D, Blank S, Bindslev-Jensen C, Biedermann T, Ollert M, Hilger C. α-Gal present on both glycolipids and glycoproteins contributes to immune response in meat-allergic patients. J Allergy Clin Immunol 2022; 150:396-405.e11. [PMID: 35459547 DOI: 10.1016/j.jaci.2022.02.030] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 02/10/2022] [Accepted: 02/21/2022] [Indexed: 10/18/2022]
Abstract
BACKGROUND The α-Gal syndrome is associated with the presence of IgE directed to the carbohydrate galactose-α-1,3-galactose (α-Gal) and is characterized by a delayed allergic reaction occurring 2 to 6 hours after ingestion of mammalian meat. On the basis of their slow digestion and processing kinetics, α-Gal-carrying glycolipids have been proposed as the main trigger of the delayed reaction. OBJECTIVE We analyzed and compared the in vitro allergenicity of α-Gal-carrying glycoproteins and glycolipids from natural food sources. METHODS Proteins and lipids were extracted from pork kidney (PK), beef, and chicken. Glycolipids were purified from rabbit erythrocytes. The presence of α-Gal and IgE binding of α-Gal-allergic patient sera (n = 39) was assessed by thin-layer chromatography as well as by direct and inhibition enzyme-linked immunosorbent assay. The in vitro allergenicity of glycoproteins and glycolipids from different meat extracts was determined by basophil activation test. Glycoprotein stability was evaluated by simulated gastric and intestinal digestion assays. RESULTS α-Gal was detected on glycolipids of PK and beef. Patient IgE antibodies recognized α-Gal bound to glycoproteins and glycolipids, although binding to glycoproteins was more potent. Rabbit glycolipids were able to strongly activate patient basophils, whereas lipid extracts from PK and beef were also found to trigger basophil activation, but at a lower capacity compared to the respective protein extracts. Simulated gastric digestion assays of PK showed a high stability of α-Gal-carrying proteins in PK. CONCLUSION Both α-Gal-carrying glycoproteins and glycolipids are able to strongly activate patient basophils. In PK and beef, α-Gal epitopes seem to be less abundant on glycolipids than on glycoproteins, suggesting a major role of glycoproteins in delayed anaphylaxis upon consumption of these food sources.
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Affiliation(s)
- Neera Chakrapani
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Jörg Fischer
- Department of Dermatology, Faculty of Medicine, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Kyra Swiontek
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg
| | | | - Farah Hannachi
- Immunology-Allergology Unit, Centre Hospitalier Luxembourg, Differdange, Luxembourg
| | - Martine Morisset
- Immunology-Allergology Unit, Centre Hospitalier Luxembourg, Differdange, Luxembourg
| | - Clément Mugemana
- Department of Materials Research and Technology, Luxembourg Institute of Science and Technology (LIST), Esch-sur-Alzette, Luxembourg
| | - Dmitry Bulaev
- Competence Center for Methodology and Statistics, LIH, Esch-sur-Alzette, Luxembourg
| | - Simon Blank
- Center of Allergy and Environment (ZAUM), Technical University of Munich, School of Medicine and Helmholtz Center Munich, German Research Center for Environment Health, Member of the Immunology and Inflammation Initiative of the Helmholtz Association, Munich, Germany
| | - Carsten Bindslev-Jensen
- Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark
| | - Tilo Biedermann
- Department of Dermatology and Allergy Biederstein, Technical University of Munich, Munich, Germany
| | - Markus Ollert
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark
| | - Christiane Hilger
- Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg.
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Abstract
Perioperative care of the patient with alpha-gal syndrome Key words: alpha-gal syndrome (AGS), red meat allergy, allergic reaction, mammalian-derived ingredients, gelatin. Overnight storage of sterile supplies Key words: sterile supplies, event-related sterility, terminal cleaning, damp dusting, instrument table. Unsterile medication cartridges Key words: dental cartridge, local anesthesia, lidocaine, alcohol, sterile field. Personnel traffic into the OR Key words: OR traffic, door openings, airflow, environmental contamination, automatic doors.
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25
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Abstract
Das Alpha-Gal-Syndrom gehört zu den spannendsten Entdeckungen in der Allergologie der letzten 15 Jahre und wird ausgelöst durch spezifisches Immunglobulin E (sIgE) gegen den für Menschen immunogenen Zucker Galaktose-α‑1,3‑Galaktose (Alpha-Gal). Säugetierfleisch, Milch und daraus hergestellte Nahrungsmittel enthalten Alpha-Gal und können zu Anaphylaxien führen. Auch Arzneimittel und Medizinprodukte aus Säugetiergewebe können allergen sein. Zeckenstiche gelten als Hauptquelle einer Induktion von Alpha-Gal-sIgE. Ziel dieses Beitrags ist es, einen Überblick über den Stand des Wissens zum klinischen Bild und zu pathophysiologischen Konzepten zu geben.
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26
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The Quantification of IgG Specific to α-Gal Could Be Used as a Risk Marker for Suffering Mammalian Meat Allergy. Foods 2022; 11:foods11030466. [PMID: 35159615 PMCID: PMC8834152 DOI: 10.3390/foods11030466] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 02/01/2022] [Accepted: 02/02/2022] [Indexed: 01/14/2023] Open
Abstract
The alpha-Gal Syndrome is a delayed meat allergy characterized by the presence of sIgE against α-Gal epitope. It is known that the α-Gal present in tick saliva induces the sensitization to this epitope ending in the production of sIgG and sIgE to α-Gal. It could be considered that the more times a person is bitten by tick species, the higher the probability of making the switch from sIgG to sIgE to α-Gal and developing allergy, but it is no clear when the switch occurs. To determine the likelihood that a subject bitten by ticks but without AGS be at risk of developing this allergy, we quantified the levels of sIgG to α-Gal by an automated system (ImmunoCap). To stablish a cut-off value for sIgG to α-Gal, a receiving operating curve (ROC) was constructed. The statistical analysis demonstrated that the risk of suffering AGS in individuals bitten by ticks was 35% when the sIgG to α-Gal was greater than or equal to 40 µg/mL. Our data indicate that the sIgG values against α-Gal could be used as a prognostic marker for developing mammalian meat allergy.
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27
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Carson AS, Gardner A, Iweala OI. Where's the Beef? Understanding Allergic Responses to Red Meat in Alpha-Gal Syndrome. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2022; 208:267-277. [PMID: 35017216 PMCID: PMC8928418 DOI: 10.4049/jimmunol.2100712] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 10/19/2021] [Indexed: 01/17/2023]
Abstract
Alpha-gal syndrome (AGS) describes a collection of symptoms associated with IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal). Individuals with AGS develop delayed hypersensitivity reactions, with symptoms occurring >2 h after consuming mammalian ("red") meat and other mammal-derived food products. The mechanisms of pathogenesis driving this paradigm-breaking food allergy are not fully understood. We review the role of tick bites in the development of alpha-gal-specific IgE and highlight innate and adaptive immune cells possibly involved in alpha-gal sensitization. We discuss the impact of alpha-gal glycosylation on digestion and metabolism of alpha-gal glycolipids and glycoproteins, and the implications for basophil and mast cell activation and mediator release that generate allergic symptoms in AGS.
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Affiliation(s)
- Audrey S. Carson
- Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology,Department of Pediatrics, University of North Carolina Food Allergy Initiative, Division of Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Aliyah Gardner
- Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology,Department of Pediatrics, University of North Carolina Food Allergy Initiative, Division of Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Onyinye I. Iweala
- Department of Medicine, Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology,Department of Pediatrics, University of North Carolina Food Allergy Initiative, Division of Allergy and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
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28
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Saretta F, Giovannini M, Mori F, Arasi S, Liotti L, Pecoraro L, Barni S, Castagnoli R, Mastrorilli C, Caminiti L, Marseglia GL, Novembre E. Alpha-Gal Syndrome in Children: Peculiarities of a "Tick-Borne" Allergic Disease. Front Pediatr 2021; 9:801753. [PMID: 35004549 PMCID: PMC8732990 DOI: 10.3389/fped.2021.801753] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 11/17/2021] [Indexed: 11/13/2022] Open
Abstract
The alpha-gal syndrome is an allergic syndrome that comprises two clinical pictures: an immediate hypersensitivity to drugs containing alpha-gal and a delayed hypersensitivity to the ingestion of red mammalian meat. This allergic syndrome is often under-recognized, and patients are mislabeled with diagnosis as spontaneous urticaria or idiopathic anaphylaxis. Even though less frequently, children could also be of interest, especially in tick-endemic areas. In most cases, a positive anamnesis for tick bites months before the onset of symptoms is recorded. The clinical manifestations could range from asymptomatic cases to severe anaphylaxis. The most frequently used diagnostic test is the determination of specific IgE for alpha-gal. Oral provocation test is usually reserved to unclear cases or to verify tolerance after diet. No long-term follow-up studies have been published, although an elimination diet could lead to a decrease of specific IgE for alpha-gal and a possible reintroduction of some avoided foods. This paper provides a literature review, focused on pediatric age, and an evaluation of available diagnostic tests. We analyze the correlation between tick bites and symptom onset and unfold the different clinical pictures to help clinicians to promptly recognized this syndrome. Lastly, we address unmet needs in this specific allergy.
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Affiliation(s)
- Francesca Saretta
- Pediatric Department, Latisana-Palmanova Hospital, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
| | - Mattia Giovannini
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Francesca Mori
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Stefania Arasi
- Translational Research in Pediatric Specialties Area, Division of Allergy, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy
| | - Lucia Liotti
- Department of Pediatrics, Salesi Children's Hospital, AOU Ospedali Riuniti Ancona, Ancona, Italy
| | - Luca Pecoraro
- Department of Medicine, University of Verona, Verona, Italy
- Maternal and Child Department, ASST Mantua, Mantova, Italy
| | - Simona Barni
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
| | - Riccardo Castagnoli
- Department of Pediatrics, Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Carla Mastrorilli
- Pediatric Unit and Emergency, University Hospital Consortium Corporation Polyclinic of Bari, Pediatric Hospital Giovanni XXIII, Bari, Italy
| | - Lucia Caminiti
- Department of Human Pathology in Adult and Development Age “Gaetano Barresi,” Allergy Unit, Department of Pediatrics, AOU Policlinico Gaetano Martino, Messina, Italy
| | - Gian Luigi Marseglia
- Department of Pediatrics, Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Elio Novembre
- Allergy Unit, Department of Pediatrics, Meyer Children's University Hospital, Florence, Italy
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29
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Villar M, Pacheco I, Mateos-Hernández L, Cabezas-Cruz A, Tabor AE, Rodríguez-Valle M, Mulenga A, Kocan KM, Blouin EF, de la Fuente J. Characterization of tick salivary gland and saliva alphagalactome reveals candidate alpha-gal syndrome disease biomarkers. Expert Rev Proteomics 2021; 18:1099-1116. [PMID: 34904495 DOI: 10.1080/14789450.2021.2018305] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Ticks are obligate hematophagous arthropods that synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) associated with the alpha-gal syndrome (AGS) or allergy to mammalian meat consumption. RESEARCH DESIGN AND METHODS In this study, we used a proteomics approach to characterize tick proteins in salivary glands (sialome SG), secreted saliva (sialome SA) and with α-Gal modification (alphagalactome SG and SA) in model tick species associated with the AGS in the United States (Amblyomma americanum) and Australia (Ixodes holocyclus). Selected proteins reactive to sera (IgE) from patients with AGS were identified to advance in the identification of possible proteins associated with the AGS. For comparative analysis, the α-Gal content was measured in various tick species. RESULTS The results confirmed that ticks produce proteins with α-Gal modifications and secreted into saliva during feeding. Proteins identified in tick alphagalactome SA by sera from patients with severe AGS symptomatology may constitute candidate disease biomarkers. CONCLUSIONS The results support the presence tick-derived proteins with α-Gal modifications in the saliva with potential implications in AGS and other disorders and protective capacity against tick infestations and pathogen infection. Future research should focus on the characterization of the function of tick glycoproteins with α-Gal in tick biology and AGS.
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Affiliation(s)
- Margarita Villar
- SaBio, Instituto de Investigación en Recursos Cinegéticos (IREC-CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13005 Ciudad Real, Spain.,Biochemistry Section, Faculty of Science and Chemical Technologies, and Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha, 13071, Ciudad Real, Spain
| | - Iván Pacheco
- SaBio, Instituto de Investigación en Recursos Cinegéticos (IREC-CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13005 Ciudad Real, Spain
| | - Lourdes Mateos-Hernández
- UMR BIPAR, INRAE, ANSES, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, 94700, France
| | - Alejandro Cabezas-Cruz
- UMR BIPAR, INRAE, ANSES, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, 94700, France
| | - Ala E Tabor
- Queensland Alliance for Agriculture & Food Innovation, Centre for Animal Science, The University of Queensland, 306 Carmody Road, St. Lucia, QLD 4072, Australia.,School of Chemistry and Molecular Biosciences, The University of Queensland, 68 Cooper Road, St. Lucia, QLD 4072, Australia
| | - Manuel Rodríguez-Valle
- Queensland Alliance for Agriculture & Food Innovation, Centre for Animal Science, The University of Queensland, 306 Carmody Road, St. Lucia, QLD 4072, Australia
| | - Albert Mulenga
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX77843, United States
| | - Katherine M Kocan
- Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA
| | - Edmour F Blouin
- Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA
| | - José de la Fuente
- SaBio, Instituto de Investigación en Recursos Cinegéticos (IREC-CSIC-UCLM-JCCM), Ronda de Toledo s/n, 13005 Ciudad Real, Spain.,Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA
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30
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Perusko M, Apostolovic D, Kiewiet MBG, Grundström J, Hamsten C, Starkhammar M, Cirkovic Velickovic T, Hage M. Bovine γ-globulin, lactoferrin, and lactoperoxidase are relevant bovine milk allergens in patients with α-Gal syndrome. Allergy 2021; 76:3766-3775. [PMID: 33938008 DOI: 10.1111/all.14889] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 03/29/2021] [Accepted: 04/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Mammalian meat is the most common trigger of the allergic reactions in patients with α-Gal syndrome (AGS). Milk and dairy, although less often, also cause a significant number of allergic manifestations. The aim of this study was to identify α-Gal-containing bovine milk proteins with allergenic properties among AGS patients. METHODS Thirty-eight AGS patients with IgE to milk were included in the study. Milk proteins were analyzed for the presence of α-Gal and for binding by patients' IgE using immunoblot, ImmunoCAP, and inhibition ELISA. Allergenicity of milk and milk proteins was assessed by basophil activation test. RESULTS More than half of the AGS patients reported allergic reactions to milk or dairy products. Bovine γ-globulin (BGG), lactoferrin (LF), and lactoperoxidase (LPO) were identified as α-Gal carrying proteins which were recognized by AGS patients' IgE. Whey mirrored the anti-α-Gal and IgE reactivity of BGG, LF, and LPO. Eighty-nine percent of the patients displayed IgE to BGG, 91% to LF, and 57% to LPO. Inhibition of α-Gal-specific IgE binding was achieved by BGG, LF, LPO, and whey. These proteins also activated AGS patients' basophils. Interestingly, at lower concentrations, LF was the most potent inhibitor of IgE binding, and the most potent activator of basophils. CONCLUSION BGG, LF, and LPO were all found to be relevant milk α-Gal-containing glycoproteins that bound AGS patients' IgE antibodies and activated their basophils. These proteins are probably involved in the allergic reactions to milk in AGS patients. LPO was for the first time shown to be an allergen.
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Affiliation(s)
- Marija Perusko
- Division of Immunology and Allergy Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
- Innovative Centre Faculty of Chemistry Belgrade Serbia
| | - Danijela Apostolovic
- Division of Immunology and Allergy Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
| | - Mensiena Berentje Geertje Kiewiet
- Division of Immunology and Allergy Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
| | - Jeanette Grundström
- Division of Immunology and Allergy Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
| | - Carl Hamsten
- Division of Immunology and Allergy Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
| | | | - Tanja Cirkovic Velickovic
- Department of Biochemistry Center of Excellence for Molecular Food Sciences University of Belgrade‐Faculty of Chemistry Belgrade Serbia
- Faculty of Bioscience Engineering Ghent University Ghent Belgium
- Ghent University Global Campus Yeonsu‐Gu, Incheon South Korea
- Serbian Academy of Sciences and Arts Belgrade Serbia
| | - Marianne Hage
- Division of Immunology and Allergy Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
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31
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Apari P, Földvári G. Tick bite induced α-gal syndrome highlights anticancer effect of allergy. Bioessays 2021; 44:e2100142. [PMID: 34811781 DOI: 10.1002/bies.202100142] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 11/03/2021] [Accepted: 11/05/2021] [Indexed: 01/05/2023]
Abstract
Tick bite induced α-gal syndrome (AGS) following consumption of mammalian meat is a recently described intriguing disease occurring worldwide. Here we argue that AGS and delayed allergy in general is an adaptive defence method against cancer. Our hypothesis synthesizes two lines of supporting evidence. First, allergy has been shown to have direct anti-cancer effects with unknown mechanism. Second, eating processed meat was shown to be linked to developing cancer. Humans lost their genes encoding molecules α-gal 30 MYA and Neu5Gc 2 MYA, the latter co-occurring with the start of using fire. These molecules are acquired from external sources, as tick bite for α-gal and mammalian meat for Neu5Gc, the latter accumulating in tumors. The resulting specific delayed allergic response is a molecular adaptation to fight cancer. By further testing and applying our hypothesis, new avenues in cancer research and therapy will open that might save lives and decrease human suffering.
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Affiliation(s)
- Péter Apari
- Institute of Evolution, Centre for Ecological Research, Budapest, Hungary
| | - Gábor Földvári
- Institute of Evolution, Centre for Ecological Research, Budapest, Hungary
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32
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Altshuler E, Krikpatrick J, Aryan M, Miralles F. Mammalian meat allergy emerges after tick bite: the alpha-gal syndrome. BMJ Case Rep 2021; 14:e245488. [PMID: 34799391 PMCID: PMC8606763 DOI: 10.1136/bcr-2021-245488] [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] [Accepted: 10/22/2021] [Indexed: 11/04/2022] Open
Abstract
Alpha-gal syndrome (AGS) is a hypersensitivity reaction to mammalian meat that develops after tick bite exposure. AGS was first described in 2009 and testing for the allergy has become available in the last decade. We report the case of a 56-year-old farmer with a history of frequent lone star tick bites who presented with a 7-year history of diffuse urticaria occurring hours after eating red meat. AGS is likely underdiagnosed because of the unusual presentation of the allergy, historic lack of available testing, and deficiency of physician knowledge about the condition. Recognition of AGS is important both to help alleviate symptom burden and to avoid iatrogenesis. Patients with AGS should not receive products containing mammalian products, such as cat-gut suture, porcine-derived heart valves, and bovine-derived vaccines. Patients with AGS may present in a variety of clinical environments and physicians of all kinds should be able to recognise the symptoms.
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Affiliation(s)
- Ellery Altshuler
- Internal Medicine, University of Florida College of Medicine, Gainesville, Florida, USA
| | | | - Mahmoud Aryan
- Internal Medicine, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA
| | - Frank Miralles
- University of Florida College of Medicine, Gainesville, Florida, USA
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33
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Alpha-gal syndrome: the first report in Poland. Cent Eur J Immunol 2021; 46:398-400. [PMID: 34764814 PMCID: PMC8574113 DOI: 10.5114/ceji.2021.108766] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 02/16/2021] [Indexed: 11/24/2022] Open
Abstract
Alpha-gal syndrome is an immunoglobulin E (IgE)-dependent allergy to galactose-α-1,3-galactose, resulting in a delayed anaphylactic reaction to red meat. The syndrome is causally linked to bites from ticks and associated with cross-reactivity to some drugs, e.g. cetuximab. Although cases of alpha-gal allergy have already been reported in a few European countries, to our best knowledge, no cases have been reported so far in Central-Eastern Europe. In the current report, we describe a case of alpha-gal syndrome diagnosed in Poland, to highlight the fact that it may occur in new geographic areas. Within three months, the described patient underwent five anaphylactic reactions with typical clinical manifestations. They developed a few hours after ingestion of red meat (pork, beef or mutton) and were preceded by tick bites. The level of specific IgE antibodies to alpha-gal reached 72.6 kAU/l, whereas the levels of specific IgE antibodies to other food allergens were within the reference range. As the onset of symptoms in this syndrome is usually delayed, numerous cases may be identified as idiopathic anaphylaxis, while early diagnosis is indispensable to avoid potentially life-threatening complications.
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34
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Ren K, Gong H, Ma Z, Tian L, Ye W, Lv X, Wu C. Structure and activity of an anti-epidermal growth factor receptor antibody without galactose-α-1,3-galactose residues. Drug Dev Res 2021; 83:637-645. [PMID: 34725841 DOI: 10.1002/ddr.21894] [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: 05/31/2021] [Revised: 09/22/2021] [Accepted: 10/03/2021] [Indexed: 11/12/2022]
Abstract
Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which has been considered as one of the key targets for cancer therapy. However, currently approved therapeutic anti-EGFR antibody may cause the hypersensitivity reaction induced by galactose-α-1,3-galactose (α-Gal) structure, which is inevitable in insect cell expression system. In this study, the Chinese hamster ovary cell line was used to produce a monoclonal antibody containing simplified glycosylation patterns (code: AB01). And cetuximab was used as a control. The two antibodies were highly similar in molecular weight, secondary structure, binding affinity and endocytosis behavior, whereas the glycotypes are extremely distinct. The flow cytometry assay suggested that AB01 induced cell cycle arrest in G1, thus inhibit cell proliferation. Moreover, both cetuximab and AB01 showed similar sensitivity for all tested cell lines in this research. In conclusion, AB01 could be a potential anti-EGFR drug candidate for cancer therapy.
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Affiliation(s)
- Keyun Ren
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.,The experimental laboratory, Beijing Institute of Radiation Medicine, Beijing, China
| | - Hao Gong
- The Innovative Drug R & D Center of Wuhan Junke-Optical Valley, Wuhan, Hubei, China
| | - Zheng Ma
- The Innovative Drug R & D Center of Wuhan Junke-Optical Valley, Wuhan, Hubei, China
| | - Lvming Tian
- The Innovative Drug R & D Center of Wuhan Junke-Optical Valley, Wuhan, Hubei, China
| | - Wei Ye
- The Innovative Drug R & D Center of Wuhan Junke-Optical Valley, Wuhan, Hubei, China
| | - Xingkai Lv
- The Innovative Drug R & D Center of Wuhan Junke-Optical Valley, Wuhan, Hubei, China
| | - Chutse Wu
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.,The experimental laboratory, Beijing Institute of Radiation Medicine, Beijing, China
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35
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36
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Bernal M, Huecker M, Shreffler J, Mittel O, Mittel J, Soliman N. Successful Treatment for Alpha Gal Mammal Product Allergy Using Auricular Acupuncture: A Case Series. Med Acupunct 2021; 33:343-348. [PMID: 35003502 DOI: 10.1089/acu.2021.0010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Introduction: Alpha gal syndrome (AGS) is an acquired allergy to mammalian products correlates with a tick bite(s) that appears to cause immune sensitization to an oligosaccharide in meat. Most publications on AGS describe no management other than avoidance of the offending agent(s). The objective of this study is to describe 2 populations of subjects who underwent Soliman Auricular Allergy Treatment (SAAT) for significant AGS meat and/or dairy allergy. Methods: We performed a retrospective review of subjects treated at 2 different medical clinics that apply the same method of auricular acupuncture (SAAT) to AGS patients. Results: A total of 137 patients presented to the 2 sites included in this study. The majority of patients were mammal product eaters before AGS; however, at the time of treatment only 7.3% of individuals (n = 10) actively consumed mammal products. Most subjects were reactive to beef (n = 135) and dairy (n = 95). The most common organ system involved in prior allergic reactions associated with AGS were gastrointestinal (n = 82, 59.9%) and dermatologic (n = 61, 44.5%). For those individuals with available outcome data on SAAT effectiveness (n = 126), 121 (96%) patients indicated that their symptoms were in remission after SAAT. Five individuals indicated that their symptoms were not in remission. Eleven individuals were unsure of treatment response or unable to be reached for follow-up. Conclusion: The SAAT method showed effectiveness in the large majority of patients. No adverse reactions were noted as a result of auricular acupuncture. This alternative medicine approach to AGS management should be further studied in prospective trials with laboratory confirmation both before and after the procedure. This low-risk treatment shows promise in treating a medical condition that causes distress in an increasing number of patients.
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Affiliation(s)
- Mateo Bernal
- Louisville Community Supported Acupuncture, Louisville, KY, USA
| | - Martin Huecker
- Department of Emergency Medicine, University of Louisville School of Medicine, Louisville, KY, USA
| | - Jacob Shreffler
- Department of Emergency Medicine, University of Louisville School of Medicine, Louisville, KY, USA
| | - Olivia Mittel
- Pediatrics, Medical Student Affairs, University of Louisville School of Medicine, Louisville, KY, USA
| | - Joseph Mittel
- Arizona Asthma and Allergy Institute, Scottsdale, AZ, USA
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Wolfe RC, Blunt J. Perioperative Considerations for the Emerging Alpha-gal Allergy. J Perianesth Nurs 2021; 36:435-437. [PMID: 34419223 DOI: 10.1016/j.jopan.2021.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 05/16/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Rachel C Wolfe
- Department of Pharmacy, Barnes-Jewish Hospital, St. Louis, MO.
| | - Jeffrey Blunt
- Department of Pharmacy, Barnes-Jewish Hospital, St. Louis, MO
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Menzies SK, Thomas AO, Tianyi FL, Abubakar SB, Nasidi A, Durfa N, Patel R, Trelfa A, Lalloo DG, Habib AG, Harrison RA. Livestock herding and Fulani ethnicity are a combined risk factor for development of early adverse reactions to antivenom treatment: Findings from a cross-sectional study in Nigeria. PLoS Negl Trop Dis 2021; 15:e0009518. [PMID: 34383742 PMCID: PMC8384187 DOI: 10.1371/journal.pntd.0009518] [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: 04/03/2021] [Revised: 08/24/2021] [Accepted: 05/29/2021] [Indexed: 12/05/2022] Open
Abstract
Background Adverse reactions to antivenom considerably complicate the clinical management of snakebite envenomed patients because it necessitates a temporary suspension of life-saving antivenom, increases costs and can compromise patient outcomes. This study sought to explore the association between cattle-herding occupation and ethnic group and the occurrence of early adverse reactions to antivenom. Methods This cross-sectional study was conducted between the 25th April and 11th July 2011 at the Kaltungo General Hospital in north east Nigeria. The exposure variable of cattle-herding occupation showed a strong correlation with the ethnic group variable, thus these were combined into a new variable with three categories (Fulani and herder, either Fulani or herder, and neither Fulani nor herder). The outcome variable was the occurrence of early adverse reactions, defined as any new symptoms occurring within 6 hours of antivenom administration. Odds Ratios were estimated using multivariable logistic regression models controlling for potential confounders. Results Among 231 envenomed snakebite victims, the overall incidence of early adverse reactions was 11.9% (95% confidence intervals: 8.0–16.9%). Patients who were Fulani and herders had a higher incidence of early adverse reactions compared to patients who were neither Fulani nor herders (20% vs 5.7%). After adjusting for age and gender, victims who were Fulani and herders were 5.9 times more likely to have an early adverse reaction, compared to victims who were neither Fulani nor herders (95% CI: 1.88–18.59; p = 0.002). Interpretation To the best of our knowledge, this is the first study to provide evidence of higher odds of early adverse reactions among patients from a particular occupation and/or ethnic group. We recommend that snake envenomed patients of Fulani origin be especially closely monitored for adverse reactions, that hospitals receiving these patients be appropriately resourced to manage both envenoming and adverse reactions and that premedication with adrenaline should be considered. Our findings provide an argument for speculation on the influence of immunological or lifestyle-related differences on the occurrence of early adverse reactions to antivenom. Antivenom is the first-choice treatment of systemic snake envenoming that annually affects between 1.8–2.7 million victims globally. Access to antivenom is especially poor for those in greatest need because they typically reside in impoverished, rural tropical communities dependent upon health facilities with limited resources. In addition, clinical treatment of snakebite victims is further complicated by early adverse reactions (EARs) to antivenom-treatment. The causes of antivenom-associated EARs are poorly understood and under-researched. Despite antivenom producers instituting costly remedial manufacturing steps (removal of pyrogens and other impurities) to make their products safer, EARs still affect a high proportion of antivenom-treated patients. Instigated by anecdotal observations to the corresponding author from clinicians in rural Nigerian hospitals that snakebite victims of cattle-herding occupation, and especially those of Fulani ethnicity, suffer more frequent EARs than other groups, this cross-sectional study identified that risks of developing EARs to antivenom treatment include the ethnicity and pastoral lifestyle of snakebite patients. To our knowledge, this is the first study to identify that EARs to antivenom-treatment include factors associated with the victim, as well as factors related to the antivenom itself. We emphasise the need for more research on the causes of adverse reactions to antivenom so that strategies to reduce incidence can be implemented.
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Affiliation(s)
- Stefanie K Menzies
- Centre for Snakebite Research and Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.,Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Aniekan O Thomas
- Centre for Snakebite Research and Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Frank-Leonel Tianyi
- Centre for Snakebite Research and Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.,Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | | | | | - Nandul Durfa
- Special Projects Unit, Federal Ministry of Health, Abuja, Nigeria
| | - Rohit Patel
- Centre for Snakebite Research and Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.,Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - Anna Trelfa
- Centre for Snakebite Research and Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | - David G Lalloo
- Centre for Snakebite Research and Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.,Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
| | | | - Robert A Harrison
- Centre for Snakebite Research and Interventions, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.,Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
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Platts‐Mills TA, Hilger C, Jappe U, van Hage M, Gadermaier G, Spillner E, Lidholm J, Keshavarz B, Aalberse RC, van Ree R, Goodman RE, Pomés A. Carbohydrate epitopes currently recognized as targets for IgE antibodies. Allergy 2021; 76:2383-2394. [PMID: 33655520 DOI: 10.1111/all.14802] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 02/17/2021] [Accepted: 02/26/2021] [Indexed: 12/11/2022]
Abstract
Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub-Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE-binding glycans recognized up to 2008 were considered to be "classical" cross-reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE-binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose-alpha-1,3-galactose (alpha-gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha-gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross-reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub-Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.
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Affiliation(s)
- Thomas A. Platts‐Mills
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Division of Allergy and Immunology University of Virginia Charlottesville Virginia USA
| | - Christiane Hilger
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Department of Infection and Immunity Luxembourg Institute of Health Esch‐sur‐Alzette Luxembourg
| | - Uta Jappe
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Division of Clinical and Molecular Allergology, Research Center Borstel AirwayResearch Center North (ARCN)German Center for Lung Research Borstel Germany
- Interdisciplinary Allergy Outpatient Clinic, Department of Internal Medicine and Pneumology University of Lübeck Lübeck Germany
| | - Marianne van Hage
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Department of Medicine Solna, Division of Immunology and Allergy Karolinska Institutet & Karolinska University Hospital Stockholm Sweden
| | - Gabriele Gadermaier
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Department of Biosciences Paris Lodron University of Salzburg Salzburg Austria
| | - Edzard Spillner
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Department of Biological and Chemical Engineering Aarhus University Denmark
| | - Jonas Lidholm
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Thermo Fisher Scientific Uppsala Sweden
| | - Behnam Keshavarz
- Division of Allergy and Immunology University of Virginia Charlottesville Virginia USA
| | - Rob C. Aalberse
- Department of Immunopathology Sanquin Amsterdam The Netherlands
| | - Ronald van Ree
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Departments of Experimental Immunology and of Otorhinolaryngology Amsterdam University Medical Centers, Academic Medical Center Amsterdam The Netherlands
| | - Richard E. Goodman
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Food Allergy Research & Resource Program University of Nebraska Lincoln Nebraska USA
| | - Anna Pomés
- WHO/IUIS Allergen Nomenclature Sub‐Committee
- Basic Research, Indoor Biotechnologies, Inc. Charlottesville Virginia USA
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Keshavarz B, Erickson LD, Platts-Mills TAE, Wilson JM. Lessons in Innate and Allergic Immunity From Dust Mite Feces and Tick Bites. FRONTIERS IN ALLERGY 2021; 2:692643. [PMID: 35387017 PMCID: PMC8974698 DOI: 10.3389/falgy.2021.692643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 06/03/2021] [Indexed: 11/13/2022] Open
Abstract
Allergic diseases represent a major cause of morbidity in modern industrialized and developing countries. The origins and development of allergic immune responses have proven difficult to unravel and remain an important scientific objective. House dust mites (HDM) and ticks represent two important causes of allergic disease. Investigations into HDM fecal particles and tick bites have revealed insights which have and will continue to shape our understanding of allergic immunity. In the present review, focus is given to the role of innate immunity in shaping the respective responses to HDM and ticks. The HDM fecal particle represents a rich milieu of molecules that can be recognized by pathogen-recognition receptors of the innate immune system. Factors in tick saliva and/or tissue damage resultant from tick feeding are thought to activate innate immune signaling that promotes allergic pathways. Recent evidence indicates that innate sensing involves not only the direct recognition of allergenic agents/organisms, but also indirect sensing of epithelial barrier disruption. Although fecal particles from HDM and bites from ticks represent two distinct causes of sensitization, both involve a complex array of molecules that contribute to an innate response. Identification of specific molecules will inform our understanding of the mechanisms that contribute to allergic immunity, however the key may lie in the combination of molecules delivered to specific sites in the body.
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Affiliation(s)
- Behnam Keshavarz
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Loren D. Erickson
- Beirne B. Carter Center for Immunology Research and the Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, United States
| | - Thomas A. E. Platts-Mills
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Jeffrey M. Wilson
- Division of Allergy and Immunology, Department of Medicine, University of Virginia, Charlottesville, VA, United States
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Schulz A, Buratto E, Konstantinov IE. Commentary: From Old World monkeys to New World humans-Evolved protection from tick bites and bioprosthetic material. JTCVS OPEN 2021; 6:97-98. [PMID: 36003557 PMCID: PMC9390648 DOI: 10.1016/j.xjon.2021.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 03/26/2021] [Accepted: 03/29/2021] [Indexed: 11/29/2022]
Affiliation(s)
- Antonia Schulz
- Department of Cardiac Surgery, Royal Children's Hospital, Melbourne, Australia
| | - Edward Buratto
- Department of Cardiac Surgery, Royal Children's Hospital, Melbourne, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, Australia
- Heart Research Group, Murdoch Children's Research Institute, Melbourne, Australia
| | - Igor E. Konstantinov
- Department of Cardiac Surgery, Royal Children's Hospital, Melbourne, Australia
- Department of Paediatrics, University of Melbourne, Melbourne, Australia
- Heart Research Group, Murdoch Children's Research Institute, Melbourne, Australia
- Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine, Melbourne, Australia
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42
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Choudhary SK, Karim S, Iweala OI, Choudhary S, Crispell G, Sharma SR, Addison CT, Kulis M, Herrin BH, Little SE, Commins SP. Tick salivary gland extract induces alpha-gal syndrome in alpha-gal deficient mice. IMMUNITY INFLAMMATION AND DISEASE 2021; 9:984-990. [PMID: 34034363 PMCID: PMC8342229 DOI: 10.1002/iid3.457] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 02/08/2021] [Accepted: 03/15/2021] [Indexed: 12/29/2022]
Abstract
Introduction Alpha‐gal syndrome (AGS) is characterized by delayed hypersensitivity to non‐primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose‐alpha‐1,3‐galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha‐gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS. Methods Eight‐ to ten‐weeks old mice with a targeted inactivation of alpha‐1,3‐galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days 0, 7, 21, 28, 42, and 49. Total IgE and alpha‐gal sIgE were quantitated on Day 56 by enzyme‐linked immunosorbent assay. Mice were challenged orally with 400 mg of cooked pork kidney homogenate or pork fat. Reaction severity was assessed by measuring a drop in core body temperature and scoring allergic signs. Results Compared to control animals, mice treated with TSGE had 190‐fold higher total IgE on Day 56 (0.60 ± 0.12 ng/ml vs. 113.2 ± 24.77 ng/ml; p < 0.001). Alpha‐gal sIgE was also produced in AGKO mice following TSGE sensitization (undetected vs. 158.4 ± 72.43 pg/ml). Further, sensitized mice displayed moderate clinical allergic signs along with a drop in core body temperature of ≥2°C as an objective measure of a systemic allergic reaction. Interestingly, female mice had higher total IgE responses to TSGE treatment but male mice had larger declines in mean body temperature. Conclusion TSGE‐sensitized AGKO mice generate sIgE to alpha‐gal and demonstrate characteristic allergic responses to pork fat and pork kidney. In keeping with the AGS responses documented in humans, mice reacted more rapidly to organ meat than to high fat pork challenge. This mouse model establishes the central role of tick bites in the development of AGS and provides a small animal model to mechanistically study mammalian meat allergy.
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Affiliation(s)
- Shailesh K Choudhary
- Division of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Shahid Karim
- Center for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi, USA
| | - Onyinye I Iweala
- Division of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.,UNC Food Allergy Initiative, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Shivangi Choudhary
- Division of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Gary Crispell
- Center for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi, USA
| | - Surendra Raj Sharma
- Center for Molecular and Cellular Biosciences, Department of Cell and Molecular Biology, School of Biological, Environmental, and Earth Sciences, The University of Southern Mississippi, Hattiesburg, Mississippi, USA
| | - Claire T Addison
- Division of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Mike Kulis
- UNC Food Allergy Initiative, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Brian H Herrin
- Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, USA
| | - Susan E Little
- Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, Oklahoma, USA
| | - Scott P Commins
- Division of Allergy, Immunology and Rheumatology, Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina, USA.,UNC Food Allergy Initiative, Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA
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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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Binder AM, Commins SP, Altrich ML, Wachs T, Biggerstaff BJ, Beard CB, Petersen LR, Kersh GJ, Armstrong PA. Diagnostic testing for galactose-alpha-1,3-galactose, United States, 2010 to 2018. Ann Allergy Asthma Immunol 2021; 126:411-416.e1. [PMID: 33422649 PMCID: PMC10961706 DOI: 10.1016/j.anai.2020.12.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 12/13/2020] [Accepted: 12/28/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND Alpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown. OBJECTIVE To characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States. METHODS This retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee's Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates. RESULTS Overall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population. CONCLUSION More than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks.
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Affiliation(s)
- Alison M Binder
- Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado.
| | - Scott P Commins
- Division of Rheumatology, Allergy, and Immunology, University of North Carolina, Chapel Hill, North Carolina
| | | | | | - Brad J Biggerstaff
- Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado
| | - Charles B Beard
- Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado
| | - Lyle R Petersen
- Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado
| | - Gilbert J Kersh
- Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado
| | - Paige A Armstrong
- Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado
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Meier RPH, Longchamp A, Mohiuddin M, Manuel O, Vrakas G, Maluf DG, Buhler LH, Muller YD, Pascual M. Recent progress and remaining hurdles toward clinical xenotransplantation. Xenotransplantation 2021; 28:e12681. [PMID: 33759229 DOI: 10.1111/xen.12681] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 02/12/2021] [Accepted: 02/21/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Xenotransplantation has made tremendous progress over the last decade. METHODS We discuss kidney and heart xenotransplantation, which are nearing initial clinical trials. RESULTS Life sustaining genetically modified kidney xenografts can now last for approximately 500 days and orthotopic heart xenografts for 200 days in non-human primates. Anti-swine specific antibody screening, preemptive desensitization protocols, complement inhibition and targeted immunosuppression are currently being adapted to xenotransplantation with the hope to achieve better control of antibody-mediated rejection (AMR) and improve xenograft longevity. These newest advances could probably facilitate future clinical trials, a significant step for the medical community, given that dialysis remains difficult for many patients and can have prohibitive costs. Performing a successful pig-to-human clinical kidney xenograft, that could last for more than a year after transplant, seems feasible but it still has significant potential hurdles to overcome. The risk/benefit balance is progressively reaching an acceptable equilibrium for future human recipients, e.g. those with a life expectancy inferior to two years. The ultimate question at this stage would be to determine if a "proof of concept" in humans is desirable, or whether further experimental/pre-clinical advances are still needed to demonstrate longer xenograft survival in non-human primates. CONCLUSION In this review, we discuss the most recent advances in kidney and heart xenotransplantation, with a focus on the prevention and treatment of AMR and on the recipient's selection, two aspects that will likely be the major points of discussion in the first pig organ xenotransplantation clinical trials.
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Affiliation(s)
- Raphael P H Meier
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Alban Longchamp
- Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Muhammad Mohiuddin
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Oriol Manuel
- Transplantation Center, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Georgios Vrakas
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Daniel G Maluf
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Leo H Buhler
- Faculty of Science and Medicine, Section of Medicine, University of Fribourg, Fribourg, Switzerland
| | - Yannick D Muller
- Division of Immunology and Allergy, University Hospital of Lausanne, Lausanne, Switzerland
| | - Manuel Pascual
- Transplantation Center, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
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Achilli S, Berthet N, Renaudet O. Antibody recruiting molecules (ARMs): synthetic immunotherapeutics to fight cancer. RSC Chem Biol 2021; 2:713-724. [PMID: 34212148 PMCID: PMC8190906 DOI: 10.1039/d1cb00007a] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Antibody-recruiting molecules (ARMs) are one of the most promising tools to redirect the immune response towards cancer cells. In this review, we aim to highlight the recent advances in the field. We will illustrate the advantages of different ARM approaches and emphasize the importance of a multivalent presentation of the binding units. Antibody-recruiting molecules (ARMs) are one of the most promising tools to redirect the immune response towards cancer cells.![]()
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Affiliation(s)
- Silvia Achilli
- Univ. Grenoble Alpes, CNRS DCM UMR 5250 F-38000 Grenoble France
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Richards NE, Richards RD. Alpha-Gal Allergy as a Cause of Intestinal Symptoms in a Gastroenterology Community Practice. South Med J 2021; 114:169-173. [PMID: 33655311 DOI: 10.14423/smj.0000000000001223] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
OBJECTIVES Immunoglobulin E (IgE) to galactose-α-1,3-galactose (alpha-gal) is a recently appreciated cause of allergic reactions to mammalian meat and dairy. In eastern North America Lone Star tick bites are the dominant mode of sensitization. Classically the alpha-gal syndrome manifests with urticaria, gastrointestinal symptoms, and/or anaphylaxis, but increasingly there are reports of isolated gastrointestinal symptoms without other common allergic manifestations. The objective of this retrospective study was to determine the frequency of IgE to alpha-gal in patients presenting with unexplained gastrointestinal symptoms to a community gastroenterology practice, and to evaluate the symptom response to the removal of mammalian products from the diet in alpha-gal-positive individuals. METHODS An electronic medical record database was used to identify patients with alpha-gal IgE laboratory testing performed within the past 4 years. These charts were reviewed for alpha-gal test results, abdominal pain, diarrhea, nausea and vomiting, hives, bronchospasm, diagnosis of irritable bowel syndrome, postprandial exacerbation of symptoms, meat exacerbation of symptoms, patient recall of tick bite, other simultaneous gastrointestinal tract diagnoses, and clinical improvement with mammalian food product avoidance. RESULTS A total of 1112 adult patients underwent alpha-gal IgE testing and 359 (32.3%) were positive. Gastrointestinal symptoms were similar in those positive and negative for alpha-gal seroreactivity. Of the 359 alpha-gal-positive patients, 122 had follow-up data available and 82.0% of these improved on a diet free of mammalian products. Few patients reported hives (3.9%) or bronchospasm (2.2%). Serum alpha-gal IgE titers ranged from 0.1 to >100 kU/L, with an average of 3.43 kU/L and a median of 0.94 kU/L. CONCLUSIONS Clinicians practicing in the region of the Lone Star tick habitat need to be aware that patients with IgE to alpha-gal can manifest with isolated abdominal pain and diarrhea, and these patients respond well to dietary exclusion of mammalian products.
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Young I, Prematunge C, Pussegoda K, Corrin T, Waddell L. Tick exposures and alpha-gal syndrome: A systematic review of the evidence. Ticks Tick Borne Dis 2021; 12:101674. [PMID: 33529984 DOI: 10.1016/j.ttbdis.2021.101674] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 01/12/2021] [Accepted: 01/14/2021] [Indexed: 12/18/2022]
Abstract
Alpha-gal syndrome (AGS) refers to a delayed allergic reaction to galactose-α-1,3-galactose (α-Gal) that occurs following the consumption of mammalian meat or exposure to other animal-based foods and products. Increasing evidence suggests that bites from certain tick species can lead to AGS through sensitization of a person's α-Gal specific IgE levels. This systematic review aimed to summarize the published evidence on this topic to understand post-tick exposure AGS epidemiology and health outcomes. A structured search for literature in eight bibliographic databases was conducted in January, 2020. Grey literature and verification searches were also performed. The exposure of interest was tick bites, and the outcome of interest was AGS. All primary research study designs were eligible for inclusion. References were screened for relevance, and data extraction and risk-of-bias assessment were conducted on relevant studies by two independent reviewers. Data were descriptively and narratively summarized. Of 1390 references screened, 102 relevant articles (103 unique studies) were identified (published from 2009 to 2020). Most studies (76.7 %) were case report or series. These 79 studies reported on 236 post-tick exposure AGS cases from 20 different countries, mostly the United States (33.5 %), Spain (19.5 %), Sweden (18.6 %), and France (12.7 %). The mean case age was 51.3 (SD = 16.7, range 5-85, n = 229), while 68.1 % were male (n = 226). The most commonly reported symptom was urticaria (71.2 %); 51.7 % of cases reported anaphylaxis. Twenty-one observational studies were reported, mostly (95.2 %) among clinical allergy patients. The proportion of AGS cases that recalled tick bites was highly variable across these studies. Three challenge studies evaluating tick exposures and α-Gal levels in α-Gal deficient mice were identified. The existing evidence suggests tick bites lead to α-Gal-specific IgE sensitization, which can cause AGS, but further research is needed to clarify if AGS is only attributable to certain tick species and whether other vectors may trigger AGS. Additional research is needed on risk factors for AGS development, evaluation of diagnostic immunoassays, and the epidemiology and distribution of AGS in different populations. Climate change will likely lead to future cases of AGS in new regions worldwide due to the predicted alteration of suitable tick habitats.
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Affiliation(s)
- Ian Young
- School of Occupational and Public Health, Ryerson University, 350 Victoria Street, Toronto, Ontario, M5B 2K3, Canada.
| | - Chatura Prematunge
- National Microbiology Laboratory, Public Health Agency of Canada, Guelph, Ontario, N1G 5B2, Canada
| | - Kusala Pussegoda
- National Microbiology Laboratory, Public Health Agency of Canada, Guelph, Ontario, N1G 5B2, Canada
| | - Tricia Corrin
- National Microbiology Laboratory, Public Health Agency of Canada, Guelph, Ontario, N1G 5B2, Canada
| | - Lisa Waddell
- National Microbiology Laboratory, Public Health Agency of Canada, Guelph, Ontario, N1G 5B2, Canada
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Kappler K, Hennet T. Emergence and significance of carbohydrate-specific antibodies. Genes Immun 2020; 21:224-239. [PMID: 32753697 PMCID: PMC7449879 DOI: 10.1038/s41435-020-0105-9] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/14/2020] [Accepted: 07/22/2020] [Indexed: 12/14/2022]
Abstract
Carbohydrate-specific antibodies are widespread among all classes of immunoglobulins. Despite their broad occurrence, little is known about their formation and biological significance. Carbohydrate-specific antibodies are often classified as natural antibodies under the assumption that they arise without prior exposure to exogenous antigens. On the other hand, various carbohydrate-specific antibodies, including antibodies to ABO blood group antigens, emerge after the contact of immune cells with the intestinal microbiota, which expresses a vast diversity of carbohydrate antigens. Here we explore the development of carbohydrate-specific antibodies in humans, addressing the definition of natural antibodies and the production of carbohydrate-specific antibodies upon antigen stimulation. We focus on the significance of the intestinal microbiota in shaping carbohydrate-specific antibodies not just in the gut, but also in the blood circulation. The structural similarity between bacterial carbohydrate antigens and surface glycoconjugates of protists, fungi and animals leads to the production of carbohydrate-specific antibodies protective against a broad range of pathogens. Mimicry between bacterial and human glycoconjugates, however, can also lead to the generation of carbohydrate-specific antibodies that cross-react with human antigens, thereby contributing to the development of autoimmune disorders.
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Affiliation(s)
| | - Thierry Hennet
- Institute of Physiology, University of Zurich, Zurich, Switzerland.
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de la Fuente J, Cabezas-Cruz A, Pacheco I. Alpha-gal syndrome: challenges to understanding sensitization and clinical reactions to alpha-gal. Expert Rev Mol Diagn 2020; 20:905-911. [PMID: 32628573 DOI: 10.1080/14737159.2020.1792781] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION The α-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody response against the carbohydrate Galα1-3Galβ1-4GlcNAc-R (α-Gal). Tick bites are recognized as the most important cause of anti-α-Gal IgE antibody increase in humans. Several risk factors have been associated with the development of AGS, but their integration into a standardized disease diagnosis has proven challenging. AREAS COVERED Herein we discuss the current AGS diagnosis based on anti-α-Gal IgE titers and propose an algorithm that considers all co-factors in the clinical history of α-Gal-sensitized patients to be incorporated into the AGS diagnosis. The need for identification of host-derived gene markers and tick-derived proteins for the diagnosis of the AGS is also discussed. EXPERT OPINION The current AGS diagnosis based on anti-α-Gal IgE titers has limitations because not all patients sensitized to α-Gal and with anti-α-Gal IgE antibodies higher than the cutoff (0.35 IU/ml) develop anaphylaxis to mammalian meat and AGS. The basophil activation test proposed to differentiate between patients with AGS and asymptomatic α-Gal sensitization cannot be easily implemented as a generalized clinical test. In coming years, the algorithm proposed here could be used in a mobile application for easier AGS diagnosis in the clinical practice.
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Affiliation(s)
- José de la Fuente
- SaBio. Instituto De Investigación En Recursos Cinegéticos IREC-CSIC-UCLM-JCCM , Ciudad Real, Spain.,Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University , Stillwater OK, USA
| | - Alejandro Cabezas-Cruz
- UMR BIPAR, INRAE, ANSES, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est , Maisons-Alfort, France
| | - Iván Pacheco
- SaBio. Instituto De Investigación En Recursos Cinegéticos IREC-CSIC-UCLM-JCCM , Ciudad Real, Spain
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