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1
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Liang L, Hwang AR, Shin YJ, Jeong KY, Park KH, Lee JH, Park JW. Fel d 1 specific IgE measurement for dog exclusive owners co-sensitized to dog and cat. World Allergy Organ J 2024; 17:101007. [PMID: 39698163 PMCID: PMC11652762 DOI: 10.1016/j.waojou.2024.101007] [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: 08/27/2024] [Revised: 10/24/2024] [Accepted: 11/11/2024] [Indexed: 12/20/2024] Open
Abstract
Background The diagnosis of the culprit allergen depends on exposure, symptoms at exposure, and the presence of specific IgE (sIgE). Pet allergens are sticky and can sensitize individuals without adoption history. Exclusive dog owners frequently exhibit both dog (e5) and cat dander sIgE (e1). We assessed whether the measurement of Fel d 1 sIgE (e94) can discriminate true cat sensitization from false positivity by cross-reactivity in the exclusive dog owners. Methods Thirty-one patients with respiratory allergies who exclusively owned dogs were enrolled for this study. e5, e1, and e94 were measured with ImmunoCAP. ELISA inhibition was performed to assess cross-reactivity. Results About 81% of patients (25/31) were both e5 and e1 positive, and 8 were also positive for e94. In the e94 positive, cat dander exhibited higher maximum inhibition of cat sIgE (94% vs 88%) and demonstrated lower IC50 (6.5 vs 737.9 BAU/mL) compared to dog dander. Conversely, in the e94 negative, dog dander demonstrated higher maximum inhibition of cat dander sIgE (71.9% vs 56.2%) and lower IC50 (172 vs 1947 BAU/mL) compared to cat dander. In the e94 positive, dog dander exhibited higher maximal inhibition for dog sIgE (91.5 vs 76.1%) and lower IC50 (10.6 vs 1679 BAU/mL) compared to cat dander, whereas in the e94 negative, the IC50 for cat dander could not be determined. Conclusions Genuine co-sensitization to cats is notable even in individuals who exclusively own dogs. Positive e94 results could discriminate authentic cat sensitization from false positivity by cross-reactivity in these patients, underscoring the importance of comprehensive allergy assessment.
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Affiliation(s)
- Lin Liang
- Graduate School of Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea
| | - Ah-Reum Hwang
- Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea
| | - Yoon Ji Shin
- Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyoung Yong Jeong
- Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea
| | - Kyung Hee Park
- Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae-Hyun Lee
- Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Jung-Won Park
- Institute of Allergy, Yonsei University College of Medicine, Seoul, South Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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2
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Zielinska J, Zagórska W, Krupa-Łaska A, Łyżwa K, Lewandowski Z, Kulus M, Grzela K. Efficacy and safety of low-dose sesame oral immunotherapy in paediatric patients: a protocol for a single-centre, randomised controlled trial. BMJ Open 2024; 14:e085811. [PMID: 39134434 PMCID: PMC11331968 DOI: 10.1136/bmjopen-2024-085811] [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: 02/26/2024] [Accepted: 07/19/2024] [Indexed: 08/21/2024] Open
Abstract
INTRODUCTION Sesame allergy, though with low prevalence, can result in severe, potentially life-threatening reactions and poses challenges in allergen avoidance due to hidden sources. In the majority of patients, sesame allergy persists and there is currently no effective long-term treatment available. Therefore, oral immunotherapy (OIT) is a promising alternative approach to managing sesame allergy. In this study protocol, we present a randomised controlled trial evaluating the efficacy and safety of OIT with low-dose sesame protein in paediatric patients. The study's aim is to compare OIT with a 300 mg maintenance dose of sesame protein against controls. METHODS AND ANALYSIS 39 participants aged 3-17 with IgE-mediated sesame allergy confirmed by oral food challenge will be enrolled into the study. The trial will be conducted at the Paediatric Hospital of the Medical University of Warsaw, Poland. The study comprises two arms-sesame OIT and control. In the sesame OIT group, interventions will be administered once daily for up to 18 months. During the first phase, the dose will be escalated every 2-4 weeks, and in the second phase, the maintenance dose of 300 mg sesame protein will continue for 3 months. Members of the control group will receive standard treatment, which includes an elimination diet and will remain under observation for 1 year. The primary outcome is the proportion of participants tolerating a single dose of 4000 mg of sesame protein during the final oral food challenge in the experimental group versus the control group. Secondary outcomes assess adverse events, changes in immunological parameters and the maximum tolerated doses of sesame protein in each group. ETHICS AND DISSEMINATION This study has been approved by the Ethics Committee of the Medical University of Warsaw (approval number: KB/269/2023). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. TRIAL REGISTRATION NUMBER NCT06261554.
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Affiliation(s)
- Joanna Zielinska
- Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland
| | | | - Anna Krupa-Łaska
- Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland
| | | | - Zbigniew Lewandowski
- Institute of Hygiene and Epidemiology, Medical University of Warsaw, Warsaw, Poland
| | - Marek Kulus
- Medical University of Warsaw, Warsaw, Poland
| | - Katarzyna Grzela
- Department of Pediatric Pneumonology and Allergy, Medical University of Warsaw, Warsaw, Poland
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Preda M, Popescu FD, Vassilopoulou E, Smolinska S. Allergenic Biomarkers in the Molecular Diagnosis of IgE-Mediated Wheat Allergy. Int J Mol Sci 2024; 25:8210. [PMID: 39125779 PMCID: PMC11311673 DOI: 10.3390/ijms25158210] [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: 06/19/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
IgE-mediated wheat allergy can take on various forms, including childhood food allergy to wheat, wheat-dependent exercise-induced anaphylaxis in young adults, baker's respiratory allergy/asthma in workers exposed to wheat flour inhalation, and contact urticaria that is caused by hydrolyzed wheat proteins in some cosmetics, and that is sometimes associated with a food allergy. Singleplex and multiplex immunoassays detect specific IgE antibodies to wheat allergenic molecular biomarkers such as omega-5 gliadin Tri a 19, lipid transfer protein Tri a 14, and alpha-amylase inhibitors. The fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens is a commonly used singleplex assay. Multiplex methods include the ELISA-based macroarray immunoassay using nano-bead technology and a microarray immunoassay on polymer-coated slides. Another promising diagnostic tool is the basophil activation test performed with omega-5 gliadin and other wheat protein types. Detailed comprehension of the structural and immunological features of the numerous wheat allergens significant in clinical settings is imperative for advancing diagnostic biomarkers for IgE-mediated wheat allergies.
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Affiliation(s)
- Mariana Preda
- Department of Allergology “Nicolae Malaxa” Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 022441 Bucharest, Romania; (M.P.); (F.-D.P.)
| | - Florin-Dan Popescu
- Department of Allergology “Nicolae Malaxa” Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 022441 Bucharest, Romania; (M.P.); (F.-D.P.)
| | - Emilia Vassilopoulou
- Department of Nutritional Sciences and Dietetics, School of Health Science, International Hellenic University, 57400 Thessaloniki, Greece;
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy
| | - Sylwia Smolinska
- Department of Clinical Immunology, Faculty of Medicine, Wroclaw Medical University, 51-616 Wroclaw, Poland
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van Hage M, Käck U, Asarnoj A, Konradsen JR. An update on the prevalence and diagnosis of cat and dog allergy - Emphasizing the role of molecular allergy diagnostics. Mol Immunol 2023; 157:1-7. [PMID: 36947935 DOI: 10.1016/j.molimm.2023.03.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/30/2023] [Accepted: 03/01/2023] [Indexed: 03/24/2023]
Abstract
The clinical presentation of cat and dog allergy vary from discomfort caused by rhinoconjuncitivitis to severe asthma. Exposure to allergens from these animals is ubiquitous and allergic sensitization to cat or dog affect up to 25% of all children and adults, but allergic sensitization does not always cause symptoms. The introduction of molecular-based allergy diagnostics has improved the possibility to characterize the allergic patient in greater detail. However, the full clinical potential of using molecular allergology in the diagnosis, characterization and treatment of patients with allergy to cats and dogs has not yet been established, although significant progress has been made during the last decade, which will be reviewed in detail in this paper.
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Affiliation(s)
- Marianne van Hage
- Department of Medicine Solna, Division of Immunology and Allergy, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
| | - Ulrika Käck
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden
| | - Anna Asarnoj
- Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - Jon R Konradsen
- Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
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Levina JG, Kalugina VG, Namazova-Baranova LS, Vishneva EA, Volkov KS, Efendieva KE, Alekseeva AA, Kaytukovа EV. Identification of Pollen and Food Sensitization Prevalence in Children with Different Atopic Phenotype Variants (Intermediate Study Results). PEDIATRIC PHARMACOLOGY 2022. [DOI: 10.15690/pf.v19i5.2464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background. Identification of the prevalence of pollen and food allergen molecules sensitization in children (considering regional characteristics) is relevant and crucial for personalized preventive and treatment measures development. Objective. The aim of the study is — study the prevalence of pollen and food allergen sensitization in children with different atopic phenotype variants. Methods. This cross-sectional study included 80 children aged from 4 months to 17 years 8 months with symptoms of allergic rhinitis, food allergy, atopic dermatitis living in the Moscow metropolitan area. All children were sensitized to 9 extracts of domestic, pollen and food allergens via the ImmunoCAP method, and molecular allergy diagnosis was carried out via the ImmunoCAP ISAC technology (n = 79). One patient with symptoms of allergic rhinitis during spring without any manifestations of cross-reactive food allergy received an unreadable result of ImmunoCAP ISAC. Results. The most common sensitization among all patients was to the birch pollen allergen extract — 65%, herd grass — 46%, common mugwort — 32%. The following sensitization to major allergens was most often detected according to molecular diagnosis: birch pollen Bet v 1 — 67%, herd grass Phl p 1 — 33% and Phl p 4 — 24%, and even less mugwort Art v 1 — 11%. The lowest sensitization was to the allergy component Amb a 1 of ambrosia — 8% of cases. Sensitization to wormwood pollen extract was revealed 2.5 times more often than to major components of this allergen. Spring allergic rhinitis was diagnosed in 45 children, and 27 of them had cross-reactive food allergy. Children with allergic rhinitis during the spring period (both with or without complaints on cross-reactive food allergy) most commonly had sensitization to the allergens components of hazelnut Cor a 1.0401 and apple Mal d 1, and least often to the component of the celery allergen Api g 1. Conclusion. Birch pollen is the most common primary allergen in children of the Moscow metropolitan area with allergy. Patients with spring allergic rhinitis despite the presence of cross-reactive food allergy usually have sensitization to the components of hazelnut and apple allergens.
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Affiliation(s)
- Julia G. Levina
- Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery
| | - Vera G. Kalugina
- Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery
| | - Leyla S. Namazova-Baranova
- Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; Pirogov Russian National Research Medical University
| | - Elena A. Vishneva
- Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; Pirogov Russian National Research Medical University
| | - Konstantin S. Volkov
- Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery
| | - Kamilla E. Efendieva
- Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; Pirogov Russian National Research Medical University
| | - Anna A. Alekseeva
- Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery
| | - Elena V. Kaytukovа
- Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; Pirogov Russian National Research Medical University
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Asthma and Allergy: Unravelling a Tangled Relationship with a Focus on New Biomarkers and Treatment. Int J Mol Sci 2022; 23:ijms23073881. [PMID: 35409241 PMCID: PMC8999577 DOI: 10.3390/ijms23073881] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/21/2022] [Accepted: 03/21/2022] [Indexed: 12/19/2022] Open
Abstract
Asthma is a major driver of health care costs across ages. Despite widely disseminated asthma-treatment guidelines and a growing variety of effective therapeutic options, most patients still experience symptoms and/or refractoriness to standard of care treatments. As a result, most patients undergo a further intensification of therapy to optimize symptom control with a subsequent increased risk of side effects. Raising awareness about the relevance of evaluating aeroallergen sensitizations in asthmatic patients is a key step in better informing clinical practice while new molecular tools, such as the component resolved diagnosis, may be of help in refining the relationship between sensitization and therapeutic recommendations. In addition, patient care should benefit from reliable, easy-to-measure and clinically accessible biomarkers that are able to predict outcome and disease monitoring. To attain a personalized asthma management and to guide adequate treatment decisions, it is of paramount importance to expand clinicians' knowledge about the tangled relationship between asthma and allergy from a molecular perspective. Our review explores the relevance of allergen testing along the asthma patient's journey, with a special focus on recurrent wheezing children. Here, we also discuss the unresolved issues regarding currently available biomarkers and summarize the evidence supporting the eosinophil-derived neurotoxin as promising biomarker.
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Shokouhi Shoormasti R, Rafaiani C, Fazlollahi MR, Kazemnejad A, Mahloojirad M, Moslemi M, Abbasi JM, Moin M, Pourpak Z, Mari A. Molecular Profile of Specific IgE to Allergenic Components in Allergic Adults Using Allergen Nano-Bead Array. Clin Exp Allergy 2022; 52:942-953. [PMID: 35174570 DOI: 10.1111/cea.14113] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 01/26/2022] [Accepted: 01/29/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND An increasing interest in the field of molecular diagnosis of allergy has been developed in recent years and it goes to be as the routine in-vitro protocol in allergy diagnosis. Friendly Allergen Nano-bead Array (FABER) is a new multiplex assay for the evaluation of specific IgE against 244 allergens including whole extracts and allergenic molecules. The research intended to assess the pattern of IgE sensitization to allergenic components of allergens in allergic adults using FABER 244. METHODS Sixty patients with allergic diseases entered this cross-sectional study. Specific IgE to 122 whole allergens extracts and 122 allergenic components was assessed using an allergen nano-bead array (FABER) for all patients. This test includes inhalant and food allergens. RESULTS Thirty-seven patients were male (61.7%). The mean (SD) age of patients was 30.73(±6.87) years. As the allergen nano-bead array results showed, Lolium perenne (63.3%), Phleum pretense (60%), and Platanus acerifolia (51.7%) were considered as the most common IgE-sensitizations to the aeroallergen extracts. Moreover, Lol p 1, Phl p 1.0102, and Cup a 1 were found as the most frequent allergenic components in our allergic patients. Among protein families, CCD bearing proteins, expansin, cysteine protease, and profilin families illustrated the highest allergic sensitization. CONCLUSIONS The results of the present study demonstrated that despite the higher prevalence of sensitization to Salsola kali (47.2%) using extract-based assays in the previous phase of this research, allergenic components of grasses (Lol p 1, Phl p 1.0102), Cup a 1 as well as Sal k1 as the major components of Cupressuss arizonica and Salsola kali showed the higher sensitization, respectively in adults' allergic patients using FABER test.
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Affiliation(s)
| | - Chiara Rafaiani
- Associated Centers for Molecular Allergology, CAAM, Rome, Italy
| | - Mohammad Reza Fazlollahi
- Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Anoshirvan Kazemnejad
- Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Maryam Mahloojirad
- Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Majid Moslemi
- Blood Transfusion Organization Research Center, Tehran, Iran
| | - Javid Morad Abbasi
- Asthma and Allergy Center, Tehran Medical Sciences Branch of Academic Center for Education, Culture and Research (ACECR), Tehran, Iran
| | - Mostafa Moin
- Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Pourpak
- Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Adriano Mari
- Associated Centers for Molecular Allergology, CAAM, Rome, Italy
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8
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Johnson J, Malinovschi A, Lidholm J, Petersson CJ, Nordvall L, Janson C, Alving K, Borres MP. Sensitization to storage proteins in peanut and hazelnut is associated with higher levels of inflammatory markers in asthma. Clin Mol Allergy 2020; 18:11. [PMID: 32581655 PMCID: PMC7310284 DOI: 10.1186/s12948-020-00126-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 06/16/2020] [Indexed: 11/10/2022] Open
Abstract
Background Sensitization to peanuts and hazelnuts is common among young asthmatics and can be primary or a result of cross-reactivity. Sensitization as a result of cross-reactivity to birch pollen is typically associated to tolerance or mild and local symptoms upon intake of peanut or hazelnut. Aim The aim of this study was to investigate relationships between IgE antibody responses against peanut and hazelnut components, airway and systemic inflammation markers, lung function parameters and reported food hypersensitivity in a cohort of asthmatic children and young adults. Methods A population of 408 asthmatic individuals aged 10-35 years were investigated. Information on hypersensitivity symptoms upon intake of peanut or hazelnut were recorded in a standardized questionnaire. Fraction of exhaled nitric oxide (FeNO), blood eosinophil count (B-Eos), spirometry, methacholine challenge outcome and IgE antibodies to peanut and hazelnut allergens were measured by standard clinical and laboratory methods. Results Subjects sensitized to any of the peanut (Ara h 1, 2 or 3) or hazelnut (Cor a 9 or 14) storage proteins were significantly younger (17.6 vs 21.2 years), had higher levels of FeNO (23.2 vs 16.7 ppb) and B-Eos (340 vs 170 cells/mcl) than those displaying only pollen-related cross-reactive sensitization. Levels of FeNO correlated with levels of IgE to storage proteins in children, but not in adults. Levels of B-Eos correlated with levels of IgE to all allergen components investigated in children, but only to levels of IgE to storage proteins in adults. Anaphylaxis and skin reactions upon intake of peanuts or hazelnuts were more often reported among subjects sensitized to the respective storage proteins than among those with only pollen-related cross-reactive sensitization. As compared to peanut, hazelnut was more often reported to cause gastrointestinal symptoms and less often oral cavity symptoms. Conclusions Sensitization to peanut and hazelnut storage proteins was associated with higher levels of inflammation markers and food hypersensitivity symptoms in this population of subjects with asthma.
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Affiliation(s)
- Jennifer Johnson
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Andrei Malinovschi
- Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden
| | | | | | - Lennart Nordvall
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Christer Janson
- Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - Kjell Alving
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Magnus P Borres
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.,Thermo Fisher Scientific, Uppsala, Sweden
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Krogulska A, Wood RA. Peanut allergy diagnosis: Moving from basic to more elegant testing. Pediatr Allergy Immunol 2020; 31:346-357. [PMID: 31945225 DOI: 10.1111/pai.13215] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 10/15/2019] [Accepted: 12/28/2019] [Indexed: 01/17/2023]
Abstract
Peanut allergy (PNA) is an IgE-mediated immune disorder, which merits particular attention due to its impact on the health and quality of life of millions of patients worldwide. PNA tends to develop in early life and resolves in only 20% of peanut-allergic children. It accounts for the majority of severe food-related allergic reactions. An accurate diagnosis of PNA is vital. In this review, we present the approach to the diagnosis of peanut allergy, starting from the history and proceeding to measures of overall sensitization and then to component-resolved diagnostics and oral food challenges as indicated. Additional testing in development includes basophil activation testing and determination of epitopes for peanut-allergic responses. Based on the literature, stepwise approaches and predictive models for diagnosing PNA are also presented.
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Affiliation(s)
- Aneta Krogulska
- Department of Pediatrics, Allergology and Gastroenterology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Robert A Wood
- Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, USA
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10
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Gray CL. Current Controversies and Future Prospects for Peanut Allergy Prevention, Diagnosis and Therapies. J Asthma Allergy 2020; 13:51-66. [PMID: 32021312 PMCID: PMC6970608 DOI: 10.2147/jaa.s196268] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 12/18/2019] [Indexed: 12/20/2022] Open
Abstract
Peanut allergy has increased substantially in the past few decades, both in developed and developing countries. Peanut allergy has become a major public health concern, affecting up to 1 in 50 children, with repercussions for school and airline policies. Recent research findings have shown that, contrary to the long-standing teaching of "delayed" introduction of allergens, early introduction of peanut protein is of benefit as an allergy prevention strategy, especially in high-risk cases. Ideal dose, frequency and duration of "proactive" peanut therapy for maximum protection remain to be determined in order for it to become acceptable and practical on a large scale. Logistics around widespread screening of high-risk patients remain complex. The correct diagnosis of peanut allergy is crucial and diagnostic tests have been fine-tuned in the past 2 decades in order to help differentiate true allergy from false-positive sensitization through cross-reactivity. Component-resolved diagnostics have become routinely available, and the use of basophil activation tests has increased, although standardization and availability remain issues. Future tests, including epitope testing and histamine-release assays, promise to be even more specific in ruling out false positives and reducing the need for incremental food challenges. Stringent peanut avoidance and prompt treatment of reactions remain the cornerstone of treatment. The concept of exposing the allergic body to small amounts of peanut protein in a cautious, orderly, escalating fashion in the form of desensitization has been widely applied in the past 10-15 years, mainly in the research domain, but of late spilling over into every-day practice. However, desensitization does not equate to a cure, and has significant safety concerns and practical ramifications; probably requiring lifelong-controlled peanut ingestion for ongoing protection. Further strategies to enhance the safety and efficacy of immunotherapy are under exploration, many with a non-specific immune-modifying effect. Despite recent advances in peanut allergy, we still need to go back to basics with accurate diagnosis, nutritional counselling, well-organized allergy action plans and accessible emergency kits.
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Affiliation(s)
- Claudia Liesel Gray
- Red Cross Children's Hospital and University of Cape Town, Cape Town, South Africa.,Kidsallergy Centre, Vincent Pallotti Hospital, Cape Town, South Africa
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11
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Wolthers OD. Molecular Allergy Diagnostics as an Adjunct to Conventional Diagnostics in a Secondary Pediatric Referral Center. ACTA ACUST UNITED AC 2020; 13:73-76. [PMID: 31187717 PMCID: PMC6751342 DOI: 10.2174/1872213x13666190610143439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 05/21/2019] [Accepted: 05/24/2019] [Indexed: 11/25/2022]
Abstract
Background: Several compositions for determination of specific molecular components in allergens have recently been patented. The role of Molecular Allergy (MA) diagnostics in suspected IgE mediated allergic conditions is currently debated. Guideline reports have concluded that population-based studies involving evaluation of the usefulness of MA diagnostics are needed. Objective: To evaluate the usefulness of MA diagnostics in a secondary pediatric referral center. Methods: A total of 961 children and adolescents aged 0.2-18.8 (mean 7.0) years was included in a pro-spective observational survey. Inclusion criterion was a suspected diagnosis of an IgE mediated condition based on history and clinical symptoms and signs. If a specific diagnosis could not be reached from con-ventional investigations suspected peanut allergy, birch pollen allergy and associated cross-reactivity, insect allergy and triggering allergens for specific immunotherapy were assessed by MA diagnostics. Results: Based on conventional work-up a diagnostic conclusion was established in 946 patients (98.4%). MA diagnostics were performed in 15 individuals (1.6%), 7 girls and 8 boys aged 3.2 to 17.8 (mean 10.6) years. In 8 cases a specific diagnosis was established based on MA diagnostics; in 7 cases MA diagnostics could not improve diagnosis. MA were most frequently (N = 7 (14%)) used in children with peanut allergy (N = 50). Conclusion: Most patients in a secondary pediatric referral center with suspected IgE mediated allergy can be managed by conventional diagnostic methods. MA diagnostics may be useful in small and selected subgroups as in patients with suspected peanut allergy, however, may not be helpful in all cases.
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Affiliation(s)
- Ole D Wolthers
- Asthma and Allergy Clinic, Children's Clinic Randers, Randers, Denmark
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12
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Schoos AMM, Chawes BL, Bloch J, Hansen B, Stokholm J, Bønnelykke K, Kristensen B, Bisgaard H. Children Monosensitized to Can f 5 Show Different Reactions to Male and Female Dog Allergen Extract Provocation: A Randomized Controlled Trial. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2019; 8:1592-1597.e2. [PMID: 31863911 DOI: 10.1016/j.jaip.2019.12.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 12/06/2019] [Accepted: 12/06/2019] [Indexed: 02/01/2023]
Abstract
BACKGROUND Dog dander consists of several allergenic molecules including Can f 5, which is a protein expressed in the prostate of male dogs. OBJECTIVE To investigate whether children monosensitized to Can f 5 show different reactions to provocation tests with male versus female dog dander in a double-blind randomized clinical trial. METHODS Twenty-two children (15-18 years) with a history of dog sensitization were enrolled from the COpenhagen Prospective Studies on Asthma in Childhood2000 mother-child cohort. Skin prick test, specific IgE levels to dog dander (e5), and dog components Can f 1, 2, 3, and 5 were first assessed. We subsequently performed skin prick test and conjunctival allergen provocation test using dog dander collected separately from male and female dogs. RESULTS Seven of the 22 children were monosensitized to Can f 5. Eight were sensitized to a mix of the dog components, and 7 were no longer sensitized to dog. Of the children monosensitized to Can f 5, all had a positive skin prick test result to male dog extract and 1 of 7 was also positive to female dog extract (P = .01). Furthermore, 5 of 7 had a positive conjunctival allergen provocation test result to male dog extract and 1 of 7 also reacted to the female dog extract (P = .03). There was no difference between reactions to male and female dog extract provocation in children sensitized to a mix of the dog components. CONCLUSIONS Children monosensitized to Can f 5 show different reactions to male and female dog extract provocation using both skin prick test and conjunctival allergen provocation test, suggesting tolerance to female dogs.
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Affiliation(s)
- Ann-Marie Malby Schoos
- COpenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Bo Lund Chawes
- COpenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Joakim Bloch
- COpenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Britta Hansen
- COpenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Stokholm
- COpenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Klaus Bønnelykke
- COpenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Hans Bisgaard
- COpenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
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13
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Savolainen J, Mascialino B, Pensamo E, Åberg KM, Silvan M, Borres MP, Korhonen K. Structured intervention plan including component-resolved diagnostics helps reducing the burden of food allergy among school-aged children. Pediatr Allergy Immunol 2019; 30:99-106. [PMID: 30346637 DOI: 10.1111/pai.12996] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 09/11/2018] [Accepted: 10/11/2018] [Indexed: 11/30/2022]
Abstract
BACKGROUND Food allergies can substantially burden patients and families by negatively affecting finances, social relationships, and personal perceptions of health. This study was performed under the Finnish Allergy Programme aimed at reducing avoidance diets to foods in schoolchildren by 50%. The main goal of this study was to investigate how many children could be freed from diet restrictions in a Finnish school district through a diagnostic algorithm including component-resolved diagnostics and food challenge. The secondary aim was to provide a crude estimate of the burden of the elimination food diets in the region, and the savings associated with the proposed intervention. METHODS A total of 205 children on a food avoidance diet according to the school register because of food allergy were invited into the study. One hundred and fifty-seven children were interviewed, tested for IgE to extracts and allergen components and food challenged in respective order. RESULTS After two years, 12 children still had an avoidance diet and three of them were treated successfully with sOTI; the rest suspended their avoidance diet (n = 134) or dropped out of the study (n = 11). The cost of the elimination diets was estimated in 172 700€ per year at start and 13 200€ per year at the end of the study; total savings were 128 400€ yearly. CONCLUSIONS The results demonstrate a 65% reduction of avoidance diets to foods in school-aged children, exceeding the 50% aim of the Finnish Allergy Programme. Therefore, it is possible to actively reduce the number of food allergy diagnoses that remain unmonitored in the society through a tailored diagnostic work-up.
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Affiliation(s)
- Johannes Savolainen
- Department of Pulmonary Diseases and Clinical Allergology, University of Turku and Turku University Hospital, Turku, Finland
| | | | - Elina Pensamo
- Department of Pulmonary Diseases and Clinical Allergology, University of Turku and Turku University Hospital, Turku, Finland
| | - K Magnus Åberg
- Thermo Fisher Scientific, Uppsala, Sweden.,Department of Environmental Science and Analytical Chemistry, Stockholm University, Stockholm, Sweden
| | | | - Magnus P Borres
- Thermo Fisher Scientific, Uppsala, Sweden.,Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
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14
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Magnusdottir H, Vidarsdóttir A, Ludviksson B, Clausen M, Lund S, Jensen A, Sigurdardottir S. Ara h 1 and Ara h 6 Sensitization Causes Clinical Peanut Allergy in Ara h 2-Negative Individuals. Int Arch Allergy Immunol 2018; 178:66-75. [DOI: 10.1159/000493327] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Accepted: 08/28/2018] [Indexed: 11/19/2022] Open
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15
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Käck U, Asarnoj A, Grönlund H, Borres MP, van Hage M, Lilja G, Konradsen JR. Molecular allergy diagnostics refine characterization of children sensitized to dog dander. J Allergy Clin Immunol 2018; 142:1113-1120.e9. [PMID: 29852259 DOI: 10.1016/j.jaci.2018.05.012] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 04/23/2018] [Accepted: 05/18/2018] [Indexed: 01/09/2023]
Abstract
BACKGROUND Sensitization to dog dander is an important risk factor for rhinoconjunctivitis and asthma but is not sufficient for diagnosing dog allergy. Molecular allergy diagnostics offer new opportunities for refined characterization. OBJECTIVES We sought to study the association between sensitization to all presently known dog allergen components and clinical symptoms of dog allergy in children evaluated by using nasal provocation tests (NPTs). METHODS Sixty children (age, 10-18 years) sensitized to dog dander extract underwent NPTs with dog dander extract. Measurement of IgE levels to dog dander and to Can f 1, Can f 2, Can f 3, and Can f 5 was performed with ImmunoCAP, and measurement of IgE levels to Can f 4 and Can f 6 was performed with streptavidin ImmunoCAP. An IgE level of 0.1 kUA/L or greater was considered positive. RESULTS There was an association between sensitization to an increasing number of dog allergen components and a positive nasal challenge result (P = .01). Sensitization to lipocalins (odds ratio [OR], 6.0; 95% CI, 1.04-34.5), in particular Can f 4 (OR, 6.80; 95% CI 1.84-25.2) and Can f 6 (OR, 5.69; 95% CI, 1.59-20.8), was associated with a positive NPT result. Monosensitization to Can f 5 was related to a negative NPT result (OR, 5.78; 95% CI, 1.01-33.0). CONCLUSION Sensitization to an increasing number of dog allergen components and to lipocalins is associated with dog allergy. Monosensitization to Can f 5 should not be regarded primarily as a marker for dog allergy.
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Affiliation(s)
- Ulrika Käck
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
| | - Anna Asarnoj
- Department of Medicine Solna Immunology and Allergy Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - Hans Grönlund
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Magnus P Borres
- Thermo Fisher Scientific, Uppsala, Sweden; Department of Women's & Children's Health, Uppsala University, Uppsala, Sweden
| | - Marianne van Hage
- Department of Medicine Solna Immunology and Allergy Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Gunnar Lilja
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Jon R Konradsen
- Department of Medicine Solna Immunology and Allergy Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
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16
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Eigenmann PA. Do we still need oral food challenges for the diagnosis of food allergy? Pediatr Allergy Immunol 2018; 29:239-242. [PMID: 29240247 DOI: 10.1111/pai.12845] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/06/2017] [Indexed: 12/24/2022]
Abstract
Food challenges are standard in the diagnosis in patients suspected of being allergic to food. However, their role is regularly questioned due to the time required to perform them, and to their cost and the inherent risk of severe reactions. Food challenges have been challenged by recent advances defining threshold values for food-specific IgE helping to predict the probability of having symptoms to the suspected food. Also, identification of major allergens to various highly allergenic foods such as peanuts or tree nuts has contributed to an increased accuracy of IgE testing. Altogether, these new data have contributed to a better definition of the role of oral food challenges in the diagnosis of food allergy. Oral food challenges are not outdated and remain the gold standard in the diagnosis of food allergy.
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Affiliation(s)
- Philippe A Eigenmann
- Department of Child and Adolescent, Pediatric Allergy Unit, University Hospitals of Geneva, Geneva, Switzerland
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17
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D'Auria E, Mameli C, Piras C, Cococcioni L, Urbani A, Zuccotti GV, Roncada P. Precision medicine in cow's milk allergy: proteomics perspectives from allergens to patients. J Proteomics 2018; 188:173-180. [PMID: 29408543 DOI: 10.1016/j.jprot.2018.01.018] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Revised: 01/20/2018] [Accepted: 01/30/2018] [Indexed: 02/07/2023]
Abstract
Cow's milk allergy (CMA) is one of the most common food allergies, especially during childhood. CMA is an immunological mediated adverse reaction to one or more cow's milk proteins, which are normally harmless to a non-allergic individual, as the result of a failure of oral tolerance. To make a correct diagnosis of CMA and a proper treatment is critical in clinical practice. Application of proteomics along with new bio-informatics tools in the field of food allergy is one of the hot topics presented in recent years. In the present review, we focus on recent applications of proteomics to the field of cow's milk allergy, from allergens quantification to the diagnosis, treatment and prognosis. Furthermore, we also shed a light on potential future directions and developments, that are parts of personalized medicine but also of the One Health approach. SIGNIFICANCE The field of food allergies is becoming a milestone in public health. Food allergies, in fact, can cause life-threatening reactions and profoundly influence the quality of life. Precise, fast and reliable diagnosis of food allergies, and in particular milk allergies is essential to avoid severe allergic reactions and also to prevent dangerous and eventually unnecessary dietary restrictions; but this can be difficult also due to a complex interaction of genetic background, environment, and microbiota. In this sense, proteomics represents steps toward researching food and milk allergy integrated with the clinic to improve pathophysiology, diagnosis, therapy, and prognosis.
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Affiliation(s)
- Enza D'Auria
- Department of Pediatrics, Ospedale dei Bambini V. Buzzi, Università degli Studi di Milano, Milano, Italy
| | - Chiara Mameli
- Department of Pediatrics, Ospedale dei Bambini V. Buzzi, Università degli Studi di Milano, Milano, Italy
| | - Cristian Piras
- Dipartimento di Medicina Veterinaria, Università degli Studi di Milano, 20133 Milano, Italy
| | - Lucia Cococcioni
- Department of Pediatrics, Ospedale dei Bambini V. Buzzi, Università degli Studi di Milano, Milano, Italy
| | - Andrea Urbani
- Università Cattolica del Sacro Cuore, Policlinico Gemelli, Roma, Italy; Fondazione Santa Lucia, Roma, Italy
| | - Gian Vincenzo Zuccotti
- Department of Pediatrics, Ospedale dei Bambini V. Buzzi, Università degli Studi di Milano, Milano, Italy
| | - Paola Roncada
- Istituto Sperimentale Italiano Lazzaro Spallanzani, 20133 Milano, Italy.
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18
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Patelis A, Gunnbjornsdottir M, Alving K, Borres MP, Högman M, Janson C, Malinovschi A. Allergen extract vs. component sensitization and airway inflammation, responsiveness and new-onset respiratory disease. Clin Exp Allergy 2017; 46:730-40. [PMID: 26243058 DOI: 10.1111/cea.12607] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Revised: 06/20/2015] [Accepted: 07/19/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND The absence of IgE sensitization to allergen components in the presence of sensitization to the corresponding extract has been reported, but its clinical importance has not been studied. OBJECTIVE To evaluate the clinical significance of IgE sensitization to three aeroallergen extracts and the corresponding components in relation to the development of respiratory disease. METHODS A total of 467 adults participated in the European Community Respiratory Health Survey (ECRHS) II and 302 in ECRHS III, 12 years later. IgE sensitization to allergen extract and components, exhaled nitric oxide (FeNO) and bronchial responsiveness to methacholine were measured in ECRHS II. Rhinitis and asthma symptoms were questionnaire-assessed in both ECRHS II and III. RESULTS A good overall correlation was found between IgE sensitization to extract and components for cat (r = 0.83), timothy (r = 0.96) and birch (r = 0.95). However, a substantial proportion of subjects tested IgE positive for cat and timothy allergen extracts but negative for the corresponding components (48% and 21%, respectively). Subjects sensitized to both cat extract and components had higher FeNO (P = 0.008) and more bronchial responsiveness (P = 0.002) than subjects sensitized only to the extract. Further, subjects sensitized to cat components were more likely to develop asthma (P = 0.005) and rhinitis (P = 0.007) than subjects sensitized only to cat extract. CONCLUSION Measurement of IgE sensitization to cat allergen components would seem to have a higher clinical value than extract-based measurement, as it related better to airway inflammation and responsiveness and had a higher prognostic value for the development of asthma and rhinitis over a 12-year period.
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Affiliation(s)
- A Patelis
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - M Gunnbjornsdottir
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - K Alving
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - M P Borres
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.,Thermo Fisher Scientific, Immunodiagnostics, Uppsala, Sweden
| | - M Högman
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.,Centre for Research and Development, Uppsala University/County Council of Gävleborg, Gävle, Sweden
| | - C Janson
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - A Malinovschi
- Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden
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19
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Dolgova AS, Sudina AE, Cherkashina AS, Stukolova OA. Component-resolved microarray analysis of IgE sensitization profiles to Felis catus major allergen molecules in Russian cat-allergic patients. Scandinavian Journal of Clinical and Laboratory Investigation 2017; 78:81-86. [PMID: 29228796 DOI: 10.1080/00365513.2017.1414955] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
We aimed to determine the profile of IgE reactivity to three major cat allergens, Fel d 1, Fel d 2 and Fel d 4, in cat-allergic patients in the Moscow region in Russia. sIgE levels to recombinant proteins expressed in Escherichia coli (Fel d 1 and Fel d 4) and to Fel d 2 protein purified from cat serum were measured using a microarray method developed in our laboratory. Sera from 174 anonymous subjects with a positive reaction (≥0.35 IU/mL) to cat dander extract (e1, ImmunoCAP) and 56 negative controls were used for IgE testing. Fel d 1 was recognized by 92.5%, Fel d 2 by 29.9% and Fel d 4 by 39.1% of the tested patient sera. The sensitivity to these three proteins was approximately 98% compared to cat dander extract (correlation coefficient to ImmunoCAP is 0.94 with PPV = 0.99 and NPV = 0.95). These predictive values appeared to be even more statistically significant than the divergence between the ISAC IgE test and the extract-based singleplex ImmunoCAP. The combination of the three investigated proteins (Fel d 1, Fel d 2 and Fel d 4) is suitable for in vitro molecular (serological) diagnosis of cat allergy in this region as a complement to cat dander extract. Moreover, with this method, we found distinction between Fel d 2 and other Feline sIgEs formation.
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Affiliation(s)
- Anna Sergeevna Dolgova
- a Molecular Diagnostics and Epidemiology Department , Central Research Institute of Epidemiology , Moscow , Russia
| | - Anna Evgenevna Sudina
- a Molecular Diagnostics and Epidemiology Department , Central Research Institute of Epidemiology , Moscow , Russia
| | | | - Olga Alekseevna Stukolova
- a Molecular Diagnostics and Epidemiology Department , Central Research Institute of Epidemiology , Moscow , Russia.,b Research Institute of Occupational Health , Moscow , Russia
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20
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Posa D, Hofmaier S, Arasi S, Matricardi PM. Natural Evolution of IgE Responses to Mite Allergens and Relationship to Progression of Allergic Disease: a Review. Curr Allergy Asthma Rep 2017; 17:28. [PMID: 28429303 DOI: 10.1007/s11882-017-0697-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
PURPOSE OF REVIEW Allergenic molecules of the house dust mite (HDM) are crucially important indoor allergens, contributing to allergic rhinitis and asthma around the globe. In the past years, recombinant molecules for diagnostics opened new pathways to investigate individual sensitization profiles and new chances for the prevention and treatment of HDM allergy. This review summarizes the latest findings on the evolution of IgE responses towards mite allergens. RECENT FINDINGS Several cross-sectional and longitudinal studies confirmed the role of Der p 1 and Der p 2 as major allergenic proteins of the HDM. A newly identified player is the major allergen Der p 23. Apart from identifying the early sensitization towards this molecule as a risk factor for asthma in school age, a recent longitudinal study described sensitization patterns showing that the production of IgE usually starts towards a group of initiator proteins and may stay monomolecular or expand to an oligo- or even polymolecular stage. This phenomenon also correlates to clinical symptoms. A relation between a broad sensitization pattern and symptom severity has also been shown cross-sectionally. Individual sensitization profiles towards HDM allergens provide important information to evaluate a patient's current stage and risk for clinical symptoms. This knowledge paves the way for an early and adequate prevention and/or treatment.
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Affiliation(s)
- Daniela Posa
- Department of Paediatric Pneumology & Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz, 1, 13353, Berlin, Germany
| | - Stephanie Hofmaier
- Department of Paediatric Pneumology & Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz, 1, 13353, Berlin, Germany
| | - Stefania Arasi
- Department of Paediatric Pneumology & Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz, 1, 13353, Berlin, Germany
| | - Paolo Maria Matricardi
- Department of Paediatric Pneumology & Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz, 1, 13353, Berlin, Germany.
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Abstract
PURPOSE OF REVIEW Allergen extracts are still widely used in allergy diagnosis as they are regarded as sensitive screening tools despite the fact that they may lack some minor allergens. Another drawback of extracts is their low specificity, which is due to the presence of cross-reactive allergens. Progress in allergen identification has disclosed a number of allergenic molecules of homologous sequence and structure which are present in different animal species. This review summarizes recent advances in mammalian and fish allergen identification and focuses on their clinical relevance. RECENT FINDINGS Serum albumins and parvalbumins are well-known animal panallergens. More recently several members of the lipocalin family were found to be cross-reactive between furry animals whereas in fish, additional allergens, enolase, aldolase and collagen, were found to be important and cross-reactive allergens. New epidemiological studies have analysed the prevalence and clinical relevance of mammalian and fish components. Primary sensitization can be distinguished from cross-sensitization by using marker allergens. Although substantial progress has been made in allergen identification, only few markers are commercially available for routine clinical practice.
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Affiliation(s)
- Christiane Hilger
- Department of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg.
| | - Marianne van Hage
- Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
| | - Annette Kuehn
- Department of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg
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Wichmann K, Heratizadeh A, Werfel T. In-vitro diagnostic in atopic dermatitis: Options and limitations. Allergol Select 2017; 1:150-159. [PMID: 30402613 PMCID: PMC6040009 DOI: 10.5414/alx01549e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 08/21/2012] [Indexed: 12/02/2022] Open
Abstract
Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis and different exogenous and endogenous trigger factors. One important factor is the sensitization to inhalant and/or food allergens. The detection of total IgE and specific IgE antibodies to inhalant and/or food allergens is one central aspect in diagnosing atopic dermatitis, especially if skin prick tests are not feasible. Many patients are polysensitized, but not all sensitizations are of clinical relevance. The challenge is to identify the sensitizations with clinical relevance and to initiate suitable therapeutic options. In this article we go into detail for the allergens house dust mite, pollen, food, and Malassezia sympodialis. Furthermore, the authors comment on the impact of the detection of specific IgG/IgG4 antibodies in the diagnosis of food allergy in atopic dermatitis. Moreover, new options in the in-vitro diagnostic will be explained briefly and their actual diagnostic significance in patients with atopic dermatitis will be highlighted. These options are the detection of specific IgE antibodies to recombinant allergens and the allergen chip.
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Affiliation(s)
- K Wichmann
- Abteilung für Immundermatologie und experimentelle Allergologie, Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover, Germany
| | - A Heratizadeh
- Abteilung für Immundermatologie und experimentelle Allergologie, Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover, Germany
| | - T Werfel
- Abteilung für Immundermatologie und experimentelle Allergologie, Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover, Germany
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Czaja-Bulsa G, Bulsa M. What Do We Know Now about IgE-Mediated Wheat Allergy in Children? Nutrients 2017; 9:E35. [PMID: 28054973 PMCID: PMC5295079 DOI: 10.3390/nu9010035] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 12/19/2016] [Accepted: 12/27/2016] [Indexed: 12/21/2022] Open
Abstract
IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.
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Affiliation(s)
- Grażyna Czaja-Bulsa
- Paediatrics and Paediatric Nursery Unit, Pomeranian Medical University, Żołnierska 48, Szczecin 71-210, Poland.
- Division of Paediatrics, Gastroenterology and Rheumatology of the "Zdroje" Hospital, Szczecin 70-780, Poland.
| | - Michał Bulsa
- Chair and Department of Pathology, Pomeranian Medical University, Unii Lubelskiej 1, Szczecin 71-252, Poland.
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Choi YJ, Yoon JM, Chang YS, Oh JW. Sensitization to component antigens in acute idiopathic urticaria in children. ALLERGY ASTHMA & RESPIRATORY DISEASE 2017. [DOI: 10.4168/aard.2017.5.6.331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Affiliation(s)
- Young Jin Choi
- Department of Pediatrics, Hanyang University Guri Hospital, Guri, Korea
| | - Jung Min Yoon
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Yeo Soon Chang
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
| | - Jae-Won Oh
- Department of Pediatrics, Hanyang University Guri Hospital, Guri, Korea
- Department of Pediatrics, Hanyang University College of Medicine, Seoul, Korea
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Eder K, Becker S, San Nicoló M, Berghaus A, Gröger M. Usefulness of component resolved analysis of cat allergy in routine clinical practice. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2016. [PMID: 27891156 DOI: 10.1186/s13223-016-0163-8.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Cat allergy is of great importance, and its prevalence is increasing worldwide. Cat allergens and house dust mite allergens represent the major indoor allergens; however, they are ubiquitous. Cat sensitization and allergy are known risk factors for rhinitis, bronchial hyperreactivity and asthma. Thus, the diagnosis of sensitization to cats is important for any allergist. METHODS 70 patients with positive skin prick tests for cats were retrospectively compared regarding their skin prick test results, as well as their specific immunoglobulin E antibody profiles with regard to their responses to the native cat extract, rFel d 1, nFel d 2 and rFel d 4. 35 patients were allergic to cats, as determined by positive anamnesis and/or nasal provocation with cat allergens, and 35 patients exhibited clinically non-relevant sensitization, as indicated by negative anamnesis and/or a negative nasal allergen challenge. RESULTS Native cat extract serology testing detected 100% of patients who were allergic to cats but missed eight patients who showed sensitization in the skin prick test and did not have allergic symptoms. The median values of the skin prick test, as well as those of the specific immunoglobulin E antibodies against the native cat extract, were significantly higher for allergic patients than for patients with clinically non-relevant sensitization. Component based diagnostic testing to rFel d 1 was not as reliable. Sensitization to nFel d 2 and rFel d 4 was seen only in individual patients. CONCLUSION Extract based diagnostic methods for identifying cat allergy and sensitization, such as the skin prick test and native cat extract serology, remain crucial in routine clinical practice. In our study, component based diagnostic testing could not replace these methods with regard to the detection of sensitization to cats and differentiation between allergy and sensitization without clinical relevance. However, component resolved allergy diagnostic tools have individual implications, and future studies may facilitate a better understanding of its use and subsequently may improve the clinical management of allergic patients.
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Affiliation(s)
- Katharina Eder
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
| | - Sven Becker
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Johannes-Gutenberg-University, Mainz, Germany
| | - Marion San Nicoló
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
| | - Alexander Berghaus
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
| | - Moritz Gröger
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
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26
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Eder K, Becker S, San Nicoló M, Berghaus A, Gröger M. Usefulness of component resolved analysis of cat allergy in routine clinical practice. Allergy Asthma Clin Immunol 2016; 12:58. [PMID: 27891156 PMCID: PMC5111222 DOI: 10.1186/s13223-016-0163-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 10/17/2016] [Indexed: 01/18/2023] Open
Abstract
Background Cat allergy is of great importance, and its prevalence is increasing worldwide. Cat allergens and house dust mite allergens represent the major indoor allergens; however, they are ubiquitous. Cat sensitization and allergy are known risk factors for rhinitis, bronchial hyperreactivity and asthma. Thus, the diagnosis of sensitization to cats is important for any allergist. Methods 70 patients with positive skin prick tests for cats were retrospectively compared regarding their skin prick test results, as well as their specific immunoglobulin E antibody profiles with regard to their responses to the native cat extract, rFel d 1, nFel d 2 and rFel d 4. 35 patients were allergic to cats, as determined by positive anamnesis and/or nasal provocation with cat allergens, and 35 patients exhibited clinically non-relevant sensitization, as indicated by negative anamnesis and/or a negative nasal allergen challenge. Results Native cat extract serology testing detected 100% of patients who were allergic to cats but missed eight patients who showed sensitization in the skin prick test and did not have allergic symptoms. The median values of the skin prick test, as well as those of the specific immunoglobulin E antibodies against the native cat extract, were significantly higher for allergic patients than for patients with clinically non-relevant sensitization. Component based diagnostic testing to rFel d 1 was not as reliable. Sensitization to nFel d 2 and rFel d 4 was seen only in individual patients. Conclusion Extract based diagnostic methods for identifying cat allergy and sensitization, such as the skin prick test and native cat extract serology, remain crucial in routine clinical practice. In our study, component based diagnostic testing could not replace these methods with regard to the detection of sensitization to cats and differentiation between allergy and sensitization without clinical relevance. However, component resolved allergy diagnostic tools have individual implications, and future studies may facilitate a better understanding of its use and subsequently may improve the clinical management of allergic patients.
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Affiliation(s)
- Katharina Eder
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
| | - Sven Becker
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Johannes-Gutenberg-University, Mainz, Germany
| | - Marion San Nicoló
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
| | - Alexander Berghaus
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
| | - Moritz Gröger
- Department of Oto-Rhino-Laryngology, Head & Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany
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27
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Abstract
An important issue in relation to the utility and reliability of biomarkers for asthma monitoring is how asthma is defined and characterized. What kind of asthma, or at what stage of the disease is a particular biomarker supposed to add information? Often, the purpose, or usefulness of a biomarker is not made clear. Diagnosis, severity evaluation, and monitoring are all different clinical uses for a biomarker, and confusion may arise when a biomarker is suitable for one of these but not another. When the utility of available biomarkers are discussed, these different roles need to be clarified. Our opinion is that there are four aspects of relevance to asthma, for which biomarkers are required: to diagnose allergies, to evaluate inflammation in the airways, to evaluate hyper-responsiveness, and for certain measures of lung function, such as lung clearance index. These types of biomarkers are needed for the phenotyping and monitoring of asthma. Another important role for biomarkers is, as mentioned above, to monitor asthma in order to follow treatment effects on inflammation and hyper-responsiveness as objective adjuncts to the patients' own symptom reports and lung function. This review will mainly focus on biomarkers that reflect airway inflammation. In spite of the numerous studies that have been conducted, we still have to remember that the value of biomarkers available for routine use, such as eosinophil counts in blood and sputum and exhaled nitric oxide, have to be interpreted in relation to reported symptoms and lung function. Measures of bronchial hyper-responsiveness, performed either by direct (methacholine challenge) or indirect (exercise or mannitol challenge) methods, could be considered biomarkers but will not be included in this review. On the other hand, diagnosing allergy is not usually useful for monitoring asthma although it is of fundamental importance for the interpretation of most biomarkers that are suitable for monitoring. We have therefore included the different approaches for diagnosing and evaluating allergic sensitization in this review.
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Maruyama N, Nakagawa T, Ito K, Cabanos C, Borres MP, Movérare R, Tanaka A, Sato S, Ebisawa M. Measurement of specific IgE antibodies to Ses i 1 improves the diagnosis of sesame allergy. Clin Exp Allergy 2016; 46:163-71. [PMID: 26310924 DOI: 10.1111/cea.12626] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Revised: 07/30/2015] [Accepted: 08/13/2015] [Indexed: 11/30/2022]
Abstract
BACKGROUND The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. OBJECTIVE The aim was to identify the allergen components useful to diagnose sesame-allergic children with the goal to reduce the number of OFCs needed. METHODS Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). RESULTS Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the best diagnostic performance of the allergen components in ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI, 0.826-0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95% CI, 0.589-0.805). The clinical sensitivity and specificity for the rSes i 1 ImmunoCAP test at optimal cut-off (3.96 kUA /L) were 86.1% and 85.7%, respectively. CONCLUSION AND CLINICAL RELEVANCE Sensitization to Ses i 1 is strongly associated with clinical sesame allergy. Measurement of specific IgE to rSes i 1 could reduce the numbers of OFCs needed.
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Affiliation(s)
- N Maruyama
- Laboratory of Food Quality Design and Development, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
| | - T Nakagawa
- Department of Allergy, Aichi Children's Health and Medical Center, Obu, Aichi, Japan
| | - K Ito
- Department of Allergy, Aichi Children's Health and Medical Center, Obu, Aichi, Japan
| | - C Cabanos
- Laboratory of Food Quality Design and Development, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan
| | - M P Borres
- Thermo Fisher Scientific, Uppsala, Sweden.,Department of Maternal and Child Health, Uppsala University, Uppsala, Sweden
| | - R Movérare
- Thermo Fisher Scientific, Uppsala, Sweden.,Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden
| | - A Tanaka
- Thermo Fisher Scientific, Tokyo, Japan
| | - S Sato
- Department of Allergy, Clinical Research Center for Allergology and Rheumatology, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan
| | - M Ebisawa
- Department of Allergy, Clinical Research Center for Allergology and Rheumatology, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan
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Chen Q, Zhong X, Acosta L, Divjan A, Rundle A, Goldstein IF, Miller RL, Perzanowski MS. Allergic sensitization patterns identified through latent class analysis among children with and without asthma. Ann Allergy Asthma Immunol 2016; 116:212-8. [PMID: 26945495 DOI: 10.1016/j.anai.2016.01.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Revised: 12/23/2015] [Accepted: 01/13/2016] [Indexed: 11/30/2022]
Abstract
BACKGROUND Specific patterns of allergic sensitization to common allergens may provide relevant clinical insight into asthma risk. OBJECTIVE To identify patterns of allergic sensitization based on multiple individual allergens and link these to current and persistent asthma using baseline and 3-year follow-up data. METHODS Children 7 to 8 years old with (n = 196) and without (n = 136) asthma from the New York City Neighborhood Asthma and Allergy Study were studied. IgE against a panel of 112 antigens was measured using the ISAC multiplex panel array. Latent class analysis (LCA) was used to identify patterns of allergic sensitization among the 26 most common allergens against which children had measurable IgE. The association between patterns of allergic sensitization and risk of asthma and other allergic diseases was examined. RESULTS LCA identified 4 patterns of allergic sensitization as follows: low risk of sensitization (prevalence of 53% in children with asthma and 76% in children without asthma), indoor (prevalence of 23% in children with asthma and 15% in children without asthma), pollen and indoor group 1 (prevalence of 16% in children with asthma and 5% in children without asthma), and pollen and indoor group 2 (prevalence of 9% in children with asthma and 4% in children without asthma). Compared with the low risk of sensitization pattern, children belonging to the 3 sensitized patterns had significantly higher risk of asthma at ages 7 to 8 years and 3 years later, with the highest risk for children in the pollen and indoor group 1 pattern. CONCLUSIONS LCA facilitates the study of sensitization profiles to a large number of common allergens. Analyzing patterns of allergic sensitization from multiple allergens reveals additional relevant associations with asthma than the study of a single allergen or total IgE.
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Affiliation(s)
- Qixuan Chen
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
| | - Xiaobo Zhong
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York
| | - Luis Acosta
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York
| | - Adnan Divjan
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York
| | - Andrew Rundle
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
| | - Inge F Goldstein
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York
| | - Rachel L Miller
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York; Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York
| | - Matthew S Perzanowski
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York
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Patelis A, Borres MP, Kober A, Berthold M. Multiplex component-based allergen microarray in recent clinical studies. Clin Exp Allergy 2016; 46:1022-32. [PMID: 27196983 DOI: 10.1111/cea.12761] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 05/13/2016] [Accepted: 05/14/2016] [Indexed: 01/07/2023]
Abstract
During the last decades component-resolved diagnostics either as singleplex or multiplex measurements has been introduced into the field of clinical allergology, providing important information that cannot be obtained from extract-based tests. Here we review recent studies that demonstrate clinical applications of the multiplex microarray technique in the diagnosis and risk assessment of allergic patients, and its usefulness in studies of allergic diseases. The usefulness of ImmunoCAP ISAC has been validated in a wide spectrum of allergic diseases like asthma, allergic rhinoconjunctivitis, atopic dermatitis, eosinophilic esophagitis, food allergy and anaphylaxis. ISAC provides a broad picture of a patient's sensitization profile from a single test, and provides information on specific and cross-reactive sensitizations that facilitate diagnosis, risk assessment, and disease management. Furthermore, it can reveal unexpected sensitizations which may explain anaphylaxis previously categorized as idiopathic and also display for the moment clinically non-relevant sensitizations. ISAC can facilitate a better selection of relevant allergens for immunotherapy compared with extract testing. Microarray technique can visualize the allergic march and molecular spreading in the preclinical stages of allergic diseases, and may indicate that the likelihood of developing symptomatic allergy is associated with specific profiles of sensitization to allergen components. ISAC is shown to be a useful tool in routine allergy diagnostics due to its ability to improve risk assessment, to better select relevant allergens for immunotherapy as well as detecting unknown sensitization. Multiplex component testing is especially suitable for patients with complex symptomatology.
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Affiliation(s)
- A Patelis
- Departement of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - M P Borres
- Immunodiagnostics, Thermo Fisher Scientific, Uppsala, Sweden.,Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - A Kober
- Immunodiagnostics, Thermo Fisher Scientific, Uppsala, Sweden
| | - M Berthold
- Immunodiagnostics, Thermo Fisher Scientific, Uppsala, Sweden
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31
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van Veen LN, Heron M, Batstra M, van Haard PMM, de Groot H. The diagnostic value of component-resolved diagnostics in peanut allergy in children attending a Regional Paediatric Allergology Clinic. BMC Pediatr 2016; 16:74. [PMID: 27255511 PMCID: PMC4891901 DOI: 10.1186/s12887-016-0609-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 05/26/2016] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND To date, diagnosing food allergies in children still presents a diagnostic dilemma, leading to uncertainty concerning the definite diagnosis of peanut allergy, as well as to the need for strict diets and the potential need for adrenalin auto-injectors. This uncertainty in particular is thought to contribute to a lower quality of life. In the diagnostic process double-blind food challenges are considered the gold standard, but they are time-consuming as well as potentially hazardous. Other diagnostic tests have been extensively studied and among these component-resolved diagnostics appeared to present a promising alternative: Ara h2, a peanut storage protein in previous studies showed to have a significant predictive value. METHODS Sixty-two out of 72 children, with suspected peanut allergy were analyzed using serum specific IgE and/or skin prick tests and specific IgE to several components of peanut (Ara h 1, 2, 3, 6, 8, 9). Subsequently, double-blind food challenges were performed. The correlation between the various diagnostic tests and the overall outcome of the double-blind food challenges were studied, in particular the severity of the reaction and the eliciting dose. RESULTS The double-blind provocation with peanut was positive in 33 children (53 %). There was no relationship between the eliciting dose and the severity of the reaction. A statistically significant relationship was found between the skin prick test, specific IgE directed to peanut, Ara h 1, Ara h 2 or Ara h 6, and the outcome of the food challenge test, in terms of positive or negative (P < .001). However, we did not find any relationship between sensitisation to peanut extract or the different allergen components and the severity of the reaction or the eliciting dose. There was no correlation between IgE directed to Ara h 3, Ara h 8, Ara h 9 and the clinical outcome of the food challenge. CONCLUSIONS This study shows that component-resolved diagnostics is not superior to specific IgE to peanut extract or to skin prick testing. At present, it cannot replace double-blind placebo-controlled food challenges for determination of the eliciting dose or the severity of the peanut allergy in our patient group.
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Affiliation(s)
- Leonieke N van Veen
- Department of Paediatric Allergology, Reinier de Graaf Hospital, Delft, PO Box 5011, 2600, GA, The Netherlands.
| | - Michiel Heron
- Department of Medical Microbiology and Immunology, St. Elisabeth Hospital, Tilburg, The Netherlands
| | - Manou Batstra
- Medical Laboratories, Department of Immunology, Reinier de Graaf Hospital, Delft, The Netherlands
| | - Paul M M van Haard
- Medical Laboratories, Department of Clinical Chemistry, Reinier de Graaf Hospital, Delft, The Netherlands
| | - Hans de Groot
- Department of Paediatric Allergology, Reinier de Graaf Hospital, Delft, PO Box 5011, 2600, GA, The Netherlands
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Ludman S, Jafari-Mamaghani M, Ebling R, Fox AT, Lack G, Du Toit G. Pollen food syndrome amongst children with seasonal allergic rhinitis attending allergy clinic. Pediatr Allergy Immunol 2016; 27:134-40. [PMID: 26534786 DOI: 10.1111/pai.12504] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/28/2015] [Indexed: 11/28/2022]
Abstract
BACKGROUND There is limited information regarding the onset and sensitization patterns of pollen food syndrome (PFS) in children. The aim was to explore this within children referred to a specialist allergy clinic at a London Tertiary Hospital. METHODS A total of 54 patients with seasonal allergic rhinitis (SAR) were enrolled in equal numbers in three age groups; 0-5, 6-10, 11-15 years. Families completed a questionnaire on rhinitis, food symptoms and quality of life. Children underwent skin prick testing (SPT) to fresh fruits, nuts and a blood test for microarray analysis. RESULTS Clinical diagnosis of PFS was made in 26/54 (48%), increasing with age (group 1 = 3 (17%), group 2 = 9 (50%), group 3 = 14 (78%) (p = 0.03)). Microarray demonstrates children aged 2.8 years sensitized to pan-allergens and 4.5 years symptomatic to pan-allergens. Peach, cherry, carrot and strawberry SPT had the highest sensitivity and NPV at 100%. The sensitivity of PR10 molecules on microarray was 92%, PPV 62% and NPV 87%. Microarray confirmed 69% of allergens on clinical history compared to 61% by SPT. Microarray and SPT had a 19% false-negative rate. The quality-of-life data showed moderate impact across all domains, and patients with PFS were significantly more likely to have increased anxiety over time spent preparing food (p = 0.029). CONCLUSIONS We demonstrate that SAR occurs in children from 1.4 years and PFS from 4.5 years with a changing pattern of pan-allergen sensitization. Microarray and SPT have moderate concordance in confirming allergens. PFS impacts negatively on quality of life and should be assessed in all paediatric allergy patients.
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Affiliation(s)
- Sian Ludman
- Royal London Hospital, Barts Health NHS Trust, London, UK
| | | | - Rosemary Ebling
- Division of Asthma, Allergy and Lung Biology, Diagnostic Immunology, King's College London, Viapath, London, UK
| | - Adam T Fox
- Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gideon Lack
- Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - George Du Toit
- Division of Asthma, Allergy and Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, UK
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Williams P, Önell A, Baldracchini F, Hui V, Jolles S, El-Shanawany T. Evaluation of a novel automated allergy microarray platform compared with three other allergy test methods. Clin Exp Immunol 2016; 184:1-10. [PMID: 26437695 DOI: 10.1111/cei.12721] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2015] [Indexed: 02/01/2023] Open
Abstract
Microarray platforms, enabling simultaneous measurement of many allergens with a small serum sample, are potentially powerful tools in allergy diagnostics. We report here the first study comparing a fully automated microarray system, the Microtest allergy system, with a manual microarray platform, Immuno-Solid phase Allergen Chip (ISAC), and two well-established singleplex allergy tests, skin prick test (SPT) and ImmunoCAP, all tested on the same patients. One hundred and three adult allergic patients attending the allergy clinic were included into the study. All patients were tested with four allergy test methods (SPT, ImmunoCAP, Microtest and ISAC 112) and a total of 3485 pairwise test results were analysed and compared. The four methods showed comparable results with a positive/negative agreement of 81-88% for any pair of test methods compared, which is in line with data in the literature. The most prevalent allergens (cat, dog, mite, timothy, birch and peanut) and their individual allergen components revealed an agreement between methods with correlation coefficients between 0·73 and 0·95. All four methods revealed deviating individual patient results for a minority of patients. These results indicate that microarray platforms are efficient and useful tools to characterize the specific immunoglobulin (Ig)E profile of allergic patients using a small volume of serum sample. The results produced by the Microtest system were in agreement with diagnostic tests in current use. Further data collection and evaluation are needed for other populations, geographical regions and allergens.
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Affiliation(s)
- P Williams
- Department of Immunology, University Hospital of Wales, Cardiff
| | | | | | | | - S Jolles
- Department of Immunology, University Hospital of Wales, Cardiff
| | - T El-Shanawany
- Department of Immunology, University Hospital of Wales, Cardiff
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34
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Bjerg A, Winberg A, Berthold M, Mattsson L, Borres MP, Rönmark E. A population-based study of animal component sensitization, asthma, and rhinitis in schoolchildren. Pediatr Allergy Immunol 2015; 26:557-63. [PMID: 26059105 DOI: 10.1111/pai.12422] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/04/2015] [Indexed: 01/21/2023]
Abstract
BACKGROUND Animal sensitization is a major determinant of asthma in children. Component-resolved studies of unselected pediatric populations are lacking. The aim was to describe sensitization to animal components and the association with asthma and rhinitis in animal-sensitized schoolchildren. METHODS A random sample of 696 children (11-12 years) from a Swedish population-based cohort was tested for sensitization to cat, dog, and horse dander using ImmunoCAP. Sera from animal-sensitized children were further analyzed by microarray including three allergen components from cat, four from dog, and two from horse. The parents completed an expanded ISAAC questionnaire. RESULTS Of 259 animal-sensitized children (≥0.1 kUA /l), 51% were sensitized to all three, 23% to two, and 25% to one species. Current asthma and asthma symptoms following contact with cats were associated with co-sensitization to Fel d 1 and Fel d 4. This association was seen already at moderate-level sensitization (1-15 ISU) to Fel d 4, at which level most children were sensitized to Fel d 1, as well. In dog-sensitized children, the majority was sensitized to more than one dog component, and co-sensitization to Can f 5 and Can f 1/f 2 conferred the greatest risk for asthma. Sensitization to the highly cross-reactive serum albumins was uncommon and not associated with asthma. CONCLUSIONS Among schoolchildren in northern Sweden, where mite allergy is uncommon, furry animals were the primary perennial sensitizers. Asthma was associated with higher levels of component sensitization, and sensitization to more than one component from the same animal conferred the greatest risk.
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Affiliation(s)
- Anders Bjerg
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.,Department of Public Health and Clinical Medicine, Occupational and Environmental, Medicine, the OLIN Unit, Umeå University, Umeå, Sweden
| | - Anna Winberg
- Department of Clinical Sciences, Pediatrics, the OLIN Unit, Umeå University, Umeå, Sweden
| | | | | | - Magnus P Borres
- ThermoFisher Scientific, Uppsala, Sweden.,Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Eva Rönmark
- Krefting Research Centre, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Göteborg, Sweden.,Department of Public Health and Clinical Medicine, Occupational and Environmental, Medicine, the OLIN Unit, Umeå University, Umeå, Sweden
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35
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Tallar MT, Grayson MH. Component-resolved allergen testing: The new frontier. World J Transl Med 2015; 4:44-50. [DOI: 10.5528/wjtm.v4.i2.44] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 03/03/2015] [Accepted: 04/14/2015] [Indexed: 02/05/2023] Open
Abstract
The discovery that allergen specific IgE (sIgE) identified individuals who were allergic to specific allergens, revolutionized allergy and immunology. Recently, component-resolved allergen testing (CRD) has shown promise in improving the field yet again. Prior to development of CRD immunoassays, whole allergen extracts were used to detect IgE mediated allergic disease either by oral, cutaneous, or conjunctival provocation. The most widely used immunoassays detect sIgE to either whole allergen sources or individual allergic components. The use of CRD micro-assay technology (not Food and Drug Administration approved in the United States) has been used to evaluate multiple allergens in parallel. This technique allows for determination of primary vs secondary sensitizations from either close sequence homology or cross-reactive carbohydrate determinants. Published studies have shown beneficial uses in hymenoptera venom immunotherapy, anaphylaxis, and food allergy. The use of component testing for aeroallergen immunotherapy has been studied, however clinical use is hampered by lack of allergen components approved for injection. Therefore, although promising in many respects, the frontier of CRD testing requires more data before it can be widely used in clinical practice.
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36
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[Respiratory allergies in children and adolescents: the role of component-resolved diagnosis and specific immunotherapy]. Wien Med Wochenschr 2015; 165:347-53. [PMID: 26249007 DOI: 10.1007/s10354-015-0375-4] [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: 02/26/2015] [Accepted: 06/26/2015] [Indexed: 10/23/2022]
Abstract
Respiratory allergies of children and adolescents are an important issue in allergology. In parallel to increasing prevalence rates also research has rapidly been developing for the last 10 years. Today we can better understand complex systems to improve our diagnostic and therapeutic accuracy. In addition to medical history, skin-prick-testing and analysis of specific IgE to allergen extracts, component resolved diagnosis has gained importance in the last years. While being increasingly helpful in the diagnosis of insect-venom and food-allergies, component-based diagnosis can also improve the management of patients with respiratory allergies. Concerning different therapeutic approaches like allergen-avoidance or symptomatic therapy, specific immunotherapy (SIT) is one of the most interesting therapy-options, as it is still the only causal therapy available. After reasonable patient-selection and the selection of the right allergen and product, SIT has a very good risk/benefit-ration and can induce long-term immuno-tolerance to specific allergens.
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37
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Popescu FD. Cross-reactivity between aeroallergens and food allergens. World J Methodol 2015; 5:31-50. [PMID: 26140270 PMCID: PMC4482820 DOI: 10.5662/wjm.v5.i2.31] [Citation(s) in RCA: 131] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 03/25/2015] [Accepted: 04/16/2015] [Indexed: 02/07/2023] Open
Abstract
In patients with respiratory allergy, cross-reactivity between aeroallergens and foods may induce food allergy, symptoms ranging from oral allergy syndrome to severe anaphylaxis. Clinical entities due to IgE sensitization to cross-reactive aeroallergen and food allergen components are described for many sources of plant origin (pollen-food syndromes and associations, such as birch-apple, cypress-peach and celery-mugwort-spice syndromes, and mugwort-peach, mugwort-chamomile, mugwort-mustard, ragweed-melon-banana, goosefoot-melon associations), fungal origin (Alternaria-spinach syndrome), and invertebrate, mammalian or avian origin (mite-shrimp, cat-pork, and bird-egg syndromes). Clinical cases of allergic reactions to ingestion of food products containing pollen grains of specific plants, in patients with respiratory allergy to Asteraceae pollen, especially mugwort and ragweed, are also mentioned, for honey, royal jelly and bee polen dietary supplements, along with allergic reactions to foods contaminated with mites or fungi in patients with respiratory allergy to these aeroallergens. Medical history and diagnosis approach may be guided by the knowledge about the diverse cross-reacting allergens involved, and by the understanding of these clinical entities which may vary significantly or may be overlapping. The association between primary IgE sensitization with respiratory symptoms to inhaled allergens and food allergy due to cross-reactive allergen components is important to assess in allergy practice. The use of molecular-based diagnosis improves the understanding of clinically relevant IgE sensitization to cross-reactive allergen components from aeroallergen sources and foods.
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Document de consensus WAO–ARIA–GA2LEN sur le diagnostic allergologique moléculaire. REVUE FRANCAISE D ALLERGOLOGIE 2015. [DOI: 10.1016/j.reval.2014.10.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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Abstract
The literature supports the notion that carbohydrate epitopes, on their own, do not contribute significantly to the induction of allergic reactions. They bind weakly to IgE antibodies and have been termed as cross reactive carbohydrate determinants. These epitopes cause confusion in in vitro IgE testing through nonspecific cross-reactivity. Coincident with the rising trends in food allergy prevalence, there has recently been reports of anaphylaxis induced by carbohydrate epitopes. There are two distinct groups, each with unique characteristics and geographical distribution. Anaphylaxis and acute allergic reactions related to the carbohydrate galactose-α-1,3-galactose (α-Gal) epitope that are present in the monoclonal antibody, cetuximab and red meat have been described in the United States and Europe populations where tick bites have been found to be the primary sensitizer. Another carbohydrate inducing anaphylaxis is galacto-oligosaccharides in commercial milk formula which has been described in the several Asian populations including Singapore. The latter is unique in that the allergen is a pure carbohydrate. We summarize the current literature on carbohydrate-induced food allergy, and evaluate the two new groups of carbohydrate allergy that have defied previous findings on carbohydrates and their role.
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Affiliation(s)
- Jian Yi Soh
- Department of Paediatrics, Khoo Teck Puat National Children's Medical Institute, National University Hospital, Singapore 119228, Singapore. ; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Chiung Hui Huang
- Department of Paediatrics, Khoo Teck Puat National Children's Medical Institute, National University Hospital, Singapore 119228, Singapore. ; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Bee Wah Lee
- Department of Paediatrics, Khoo Teck Puat National Children's Medical Institute, National University Hospital, Singapore 119228, Singapore. ; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
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Luyt D, Ball H, Makwana N, Green MR, Bravin K, Nasser SM, Clark AT. BSACI guideline for the diagnosis and management of cow's milk allergy. Clin Exp Allergy 2014; 44:642-72. [PMID: 24588904 DOI: 10.1111/cea.12302] [Citation(s) in RCA: 226] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Revised: 02/19/2014] [Accepted: 02/26/2014] [Indexed: 12/20/2022]
Abstract
This guideline advises on the management of patients with cow's milk allergy. Cow's milk allergy presents in the first year of life with estimated population prevalence between 2% and 3%. The clinical manifestations of cow's milk allergy are very variable in type and severity making it the most difficult food allergy to diagnose. A careful age- and disease-specific history with relevant allergy tests including detection of milk-specific IgE (by skin prick test or serum assay), diagnostic elimination diet, and oral challenge will aid in diagnosis in most cases. Treatment is advice on cow's milk avoidance and suitable substitute milks. Cow's milk allergy often resolves. Reintroduction can be achieved by the graded exposure, either at home or supervised in hospital depending on severity, using a milk ladder. Where cow's milk allergy persists, novel treatment options may include oral tolerance induction, although most authors do not currently recommend it for routine clinical practice. Cow's milk allergy must be distinguished from primary lactose intolerance. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for clinicians in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking the panel of experts in the committee reached consensus. Grades of recommendation are shown throughout. The document encompasses epidemiology, natural history, clinical presentations, diagnosis, and treatment.
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Affiliation(s)
- D Luyt
- University Hospitals of Leicester NHS Trust, Leicester, UK
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41
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Ebisawa M, Movérare R, Sato S, Borres MP, Ito K. The predictive relationship between peanut- and Ara h 2-specific serum IgE concentrations and peanut allergy. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2014; 3:131-2.e1. [PMID: 25577637 DOI: 10.1016/j.jaip.2014.10.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 10/17/2014] [Accepted: 10/21/2014] [Indexed: 11/28/2022]
Affiliation(s)
- Motohiro Ebisawa
- Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Japan.
| | - Robert Movérare
- Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden; Thermo Fisher Scientific, Uppsala, Sweden
| | - Sakura Sato
- Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Japan
| | - Magnus P Borres
- Thermo Fisher Scientific, Uppsala, Sweden; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Komei Ito
- Department of Allergy, Aichi Children's Health and Medical Center, Obu, Japan
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Konradsen JR, Fujisawa T, van Hage M, Hedlin G, Hilger C, Kleine-Tebbe J, Matsui EC, Roberts G, Rönmark E, Platts-Mills TAE. Allergy to furry animals: New insights, diagnostic approaches, and challenges. J Allergy Clin Immunol 2014; 135:616-25. [PMID: 25282018 DOI: 10.1016/j.jaci.2014.08.026] [Citation(s) in RCA: 122] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 07/08/2014] [Accepted: 08/05/2014] [Indexed: 12/16/2022]
Abstract
The prevalence of allergy to furry animals has been increasing, and allergy to cats, dogs, or both is considered a major risk factor for the development of asthma and rhinitis. An important step forward in the diagnosis of allergy to furry animals has been made with the introduction of molecular-based allergy diagnostics. A workshop on furry animals was convened to provide an up-to-date assessment of our understanding of (1) the exposure and immune response to the major mammalian allergens, (2) the relationship of these responses (particularly those to specific proteins or components) to symptoms, and (3) the relevance of these specific antibody responses to current or future investigation of patients presenting with allergic diseases. In this review research results discussed at the workshop are presented, including the effect of concomitant exposures from other allergens or microorganisms, the significance of the community prevalence of furry animals, molecular-based allergy diagnostics, and a detailed discussion of cat and dog components.
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Affiliation(s)
- Jon R Konradsen
- Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
| | - Takao Fujisawa
- Institute for Clinical Research, Mie National Hospital, Mie, Japan
| | - Marianne van Hage
- Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden
| | - Gunilla Hedlin
- Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
| | - Christiane Hilger
- Laboratory of Immunogenetics and Allergology, CRP-Santé, Luxembourg, Luxembourg
| | - Jörg Kleine-Tebbe
- Allergy & Asthma Center Westend, Outpatient Clinic and Research Unit, Berlin, Germany
| | - Elizabeth C Matsui
- Division of Pediatric Allergy/Immunology, Johns Hopkins School of Medicine, Baltimore, Md
| | - Graham Roberts
- David Hide Asthma and Allergy Research Centre, St Mary's Hospital, Isle of Wight, United Kingdom; Human Development and Health and Clinical and Experimental Sciences Academic Units, University of Southampton Faculty of Medicine, Southampton, United Kingdom; NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
| | - Eva Rönmark
- Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, Umeå University, Umeå, Sweden
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Johnson J, Malinovschi A, Alving K, Lidholm J, Borres MP, Nordvall L. Ten-year review reveals changing trends and severity of allergic reactions to nuts and other foods. Acta Paediatr 2014; 103:862-7. [PMID: 24825328 DOI: 10.1111/apa.12687] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 04/16/2014] [Accepted: 05/06/2014] [Indexed: 11/28/2022]
Abstract
AIM Over the past few decades, the incidence of food allergies has risen and Sweden has increased its import of peanuts and exotic nuts, such as cashew nuts, which may cause severe allergic reactions. This study aimed to retrospectively investigate paediatric emergency visits due to food reactions over a 10-year period, focusing on reactions to peanuts and tree nuts. METHODS Emergency visits to Uppsala University Children's Hospital, Sweden, between September 2001 and December 2010, were reviewed, and cases containing diagnostic codes for anaphylaxis, allergic reactions or allergy and hypersensitivity not caused by drugs or biological substances were retrieved. RESULTS We analysed 703 emergency visits made by 578 individuals with food allergies. Peanuts and tree nuts accounted for 50% of the food allergies and were more frequently associated with adrenaline treatment and hospitalisation than other foods. Cashew nut reactions increased over the study period, and together with peanuts, they were responsible for more anaphylactic reactions than hazelnuts. CONCLUSION Peanut and tree nut reactions were more likely to result in adrenaline treatment and hospitalisation than other food reactions. Peanut and cashew nut reactions were more likely to cause anaphylaxis than hazelnuts. Cashew nut reactions increased during the study period.
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Affiliation(s)
- Jennifer Johnson
- Department of Women's and Children's Health; Uppsala University; Uppsala Sweden
| | - Andrei Malinovschi
- Department of Medical Sciences, Clinical Physiology; Uppsala University; Uppsala Sweden
| | - Kjell Alving
- Department of Women's and Children's Health; Uppsala University; Uppsala Sweden
| | | | - Magnus P Borres
- Department of Women's and Children's Health; Uppsala University; Uppsala Sweden
- Thermo Fisher Scientific; Uppsala Sweden
| | - Lennart Nordvall
- Department of Women's and Children's Health; Uppsala University; Uppsala Sweden
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Vieths S, Bieber T. [Personalised medicine for the diagnosis and treatment of allergic diseases]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2014; 56:1531-7. [PMID: 24170082 DOI: 10.1007/s00103-013-1821-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Immunoglobulin E (IgE) mediated allergic diseases are characterised by heterogeneous clinical phenotypes and a large variety of different sensitisation patterns. Apart from genetic predisposition several environmental factors play a role in sensitisation and elicitation of symptoms. Since the majority of clinically relevant allergens are now available as purified recombinant allergens component-resolved in vitro diagnosis allows the sensitization profile of allergic patients to be determined at the molecular level. Such data may allow physicians to draw conclusions on the severity and persistence of a given allergic disease and to predict the outcome of allergen-specific immunotherapy (SIT) However, the potential of this approach needs to be demonstrated in controlled clinical trials. Moreover, in the context of atopic dermatitis, allergic rhinitis, allergic bronchial asthma as well as the atopic march several screening-biomarkers, diagnostic and prognostic biomarkers, biomarkers of severity and predictive biomarkers are presented and discussed in this article. Traditionally a relevant proportion of allergen-specific immunotherapies is performed in a personalised manner using named patient products manufactured on the basis of an individual prescription. Such named patient products are often mixtures containing several allergen extracts from different sources. However, there is no proven evidence for the safety and efficacy of this approach. In Germany the Therapy Allergen Ordinance ("Therapieallergene-Verordnung", TAV) regulates that in the future allergen products for SIT of insect venom allergies, allergies to pollen of early flowering trees and grass pollen and house dust mite allergies cannot be marketed as named patient products, but always require a marketing authorisation. Thus personalised SIT with named patient products is restricted to the treatment of less prevalent allergies, for which the generation of state-of-the-art clinical data is more difficult. Several recombinant allergens are currently evaluated in phase III clinical trials. In contrast to allergen extracts recombinant allergens offer the possibility to treat patients with a precisely adjusted mixture of the disease-eliciting allergen molecules. However, the implementation of this personalised approach to SIT within the given regulatory framework represents a challenge to regulators.
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Affiliation(s)
- S Vieths
- Paul-Ehrlich-Institut, Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel, Paul-Ehrlich-Str. 51-59, 63225, Langen, Deutschland,
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Hedlin G. Management of severe asthma in childhood--state of the art and novel perspectives. Pediatr Allergy Immunol 2014; 25:111-21. [PMID: 24102748 DOI: 10.1111/pai.12112] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/10/2013] [Indexed: 11/30/2022]
Abstract
The majority of children with asthma have mild or moderate disease and can obtain adequate control of symptoms through avoidance of triggering factors and/or with the help of medications. There is still a group of children with severe asthma in whom symptom control is poor depending either on identifiable aggravating factors or on true therapy resistance. These children have a poor quality of life and are limited by the severity of their disease. There is a need for a staged approach to the assessment and treatment of this small but vulnerable and resource-consuming group. The current review will provide an overview of a possible standardized approach to characterize this heterogeneous group of severely sick children including some newly developed ways of assessing asthma severity and potentialities of new asthma therapies. Furthermore, the umbrella term 'problematic severe asthma' is described. The term encompasses children whose severe asthma is due to identifiable exacerbating factors, as well as children who are resistant to any conventional therapeutic approach. Characteristics of these two groups of children are described, as are possible biomarkers and current and emerging diagnostic tools for allergy evaluation. Some recent advances and future possibilities for treatment of severe asthma are also presented in this review.
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Affiliation(s)
- Gunilla Hedlin
- Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
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Konradsen JR, Nordlund B, Onell A, Borres MP, Grönlund H, Hedlin G. Severe childhood asthma and allergy to furry animals: refined assessment using molecular-based allergy diagnostics. Pediatr Allergy Immunol 2014; 25:187-92. [PMID: 24460778 DOI: 10.1111/pai.12198] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/17/2013] [Indexed: 01/01/2023]
Abstract
BACKGROUND Allergy to cats and dogs and polysensitization towards these animals are associated with severe childhood asthma. Molecular-based allergy diagnostics offers new opportunities for improved characterization and has been suggested to be particularly useful in patients with polysensitization and/or severe asthma. The aim was to use extract- and molecular-based allergy diagnostics to compare patterns of IgE sensitization towards aeroallergens in children with problematic severe and controlled asthma. METHODS Children with a positive ImmunoCAP towards any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish study on severe childhood asthma. Severe (n = 37, age 13 years) and controlled (n = 28, age 14 years) asthmatics underwent assessment of allergic sensitization by ImmunoCap (kUA /l) and immunosolid-phase allergen chip (ISAC). In addition, Asthma Control Test, spirometry and a methacholine challenge were performed. RESULTS Children with severe asthma had lower asthma control (p < 0.001) and FEV1 (p = 0.001) and more bronchial hyper-responsiveness (p = 0.008) in spite of high doses of inhaled steroids (≥800 μg budesonide). Children with severe asthma displayed higher levels of IgE antibodies towards cat (17 vs. 3.9, p = 0.027), dog (3.8 vs. 1.2, p = 0.012) and horse (7.4 vs. 0.7, p = 0.014). Sensitization towards Can f 2 (22% vs. 0%, p = 0.009) and Equ c 1 (51% vs. 25%, p = 0.03) was more common in severe asthma. IgE levels towards Equ c 1 correlated with asthma control (r = -0.41, p = 0.04). CONCLUSION Children with severe allergic asthma had higher sIgE levels to cat, dog and horse. Molecular-based allergy diagnostics revealed a more complex molecular spreading of allergen components in children with the most severe disease.
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Affiliation(s)
- Jon R Konradsen
- Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
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Czaja-Bulsa G, Bulsa M. The natural history of IgE mediated wheat allergy in children with dominant gastrointestinal symptoms. Allergy Asthma Clin Immunol 2014; 10:12. [PMID: 24572171 PMCID: PMC3939402 DOI: 10.1186/1710-1492-10-12] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2013] [Accepted: 02/16/2014] [Indexed: 12/31/2022] Open
Abstract
Background Wheat is one of the most common food allergens in children. The purpose of this study is to define the natural course of wheat allergy in children with dominant gastrointestinal symptoms and identify factors that help predict development of tolerance. Methods The prospective analysis covered 50 children with positive food challenge results (DBPCFC) and positive wheat IgE test result. Resolution of wheat allergy was determined on the basis of food challenge results (open challenge). The impact of each of the studied factors on the age when tolerance developed was assessed by means of the Cox proportional hazard regression model. Results The median age of tolerance development was 69.5 months (37-192 mo.). The rates of resolution were 20% by the age of 4 years, 52% by the age of 8 years, and 66% by 12 years, and 76% by 18 years. The median age of the tolerance development in children with peak wheat IgE level below10 kU/L was 41.4 months, with peak wheat IgE from 10 to 19.9 kU/L was 44.5 months, with peak IgE from 20 to 49.9 kU/L – 84,9 months and with peak IgE ≥ 50 kU/L – 190.5 months. The median of the age when the highest levels of IgE for wheat were reached was 33 months (2-52 mo.) in children with resolved wheat allergy and 67 months (36-178 mo.) in children with persistent allergy (p = .001). Conclusions 1. The majority of children with wheat allergy can tolerate wheat by adolescence. 2. The age when tolerance to wheat developed depended on the level and the age of reaching the highest levels of specific IgE for wheat. The higher the values of the above parameters, the older a child was when they developed tolerance to wheat.
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Affiliation(s)
- Grażyna Czaja-Bulsa
- Pediatrics and Pediatric Nursery Unit of the Pomeranian Medical University in Szczecin, Szczecin, Poland.
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Component-resolved diagnosis in pediatric allergic rhinoconjunctivitis and asthma. Curr Opin Allergy Clin Immunol 2014; 13:446-51. [PMID: 23703065 DOI: 10.1097/aci.0b013e32836274d8] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW The aim of this review is to update readers on the growing impact of a molecular approach (CRD) to the diagnosis and treatment of children with respiratory allergies RECENT FINDINGS A large panel of highly purified natural or recombinant species-specific and cross-reacting allergenic molecules is now available for clinical purposes. Species-specific molecules allow identifying specific sensitization toward a given allergenic source. Cross-reacting molecules allow interpreting polysensitization patterns that cannot be detailed using routine skin prick tests or specific IgE tests based on allergenic extracts. These molecular tools are transforming and improving the interpretation of clinical and laboratory tests used to define patients' IgE-sensitization profile. SUMMARY The accurate dissection of the IgE repertoire offers new possibilities in the diagnosis, prophylaxis and treatment of pediatric allergic rhinoconjunctivitis and asthma.
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Soares-Weiser K, Takwoingi Y, Panesar SS, Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Halken S, Poulsen L, van Ree R, Vlieg-Boerstra BJ, Sheikh A. The diagnosis of food allergy: a systematic review and meta-analysis. Allergy 2014; 69:76-86. [PMID: 24329961 DOI: 10.1111/all.12333] [Citation(s) in RCA: 145] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/24/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND We investigated the accuracy of tests used to diagnose food allergy. METHODS Skin prick tests (SPT), specific-IgE (sIgE), component-resolved diagnosis and the atopy patch test (APT) were compared with the reference standard of double-blind placebo-controlled food challenge. Seven databases were searched and international experts were contacted. Two reviewers independently identified studies, extracted data, and used QUADAS-2 to assess risk of bias. Where possible, meta-analysis was undertaken. RESULTS Twenty-four (2831 participants) studies were included. For cows' milk allergy, the pooled sensitivities were 53% (95% CI 33-72), 88% (95 % CI 76-94), and 87% (95% CI 75-94), and specificities were 88% (95% CI 76-95), 68% (95% CI 56-77), and 48% (95% CI 36-59) for APT, SPT, and sIgE, respectively. For egg, pooled sensitivities were 92% (95% CI 80-97) and 93% (95% CI 82-98), and specificities were 58% (95% CI 49-67) and 49% (40-58%) for skin prick tests and specific-IgE. For wheat, pooled sensitivities were 73% (95% CI 56-85) and 83% (95% CI 69-92), and specificities were 73% (95% CI 48-89) and 43% (95% CI 20-69%) for SPT and sIgE. For soy, pooled sensitivities were 55% (95% CI 33-75) and 83% (95% CI 64-93), and specificities were 68% (95% CI 52-80) and 38% (95% CI 24-54) for SPT and sIgE. For peanut, pooled sensitivities were 95% (95% CI 88-98) and 96% (95% CI 92-98), and specificities were 61% (95% CI 47-74), and 59% (95% CI 45-72) for SPT and sIgE. CONCLUSIONS The evidence base is limited and weak and is therefore difficult to interpret. Overall, SPT and sIgE appear sensitive although not specific for diagnosing IgE-mediated food allergy.
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Affiliation(s)
| | - Y. Takwoingi
- Public Health Epidemiology and Biostatistics; School of Health and Population Sciences; University of Birmingham; Birmingham UK
| | - S. S. Panesar
- Allergy & Respiratory Research Group; Centre for Population Health Sciences; The University of Edinburgh; Edinburgh UK
| | - A. Muraro
- Department of Pediatrics; Center for Food Allergy Diagnosis and Treatment, Veneto Region; University of Padua; Padua Italy
| | - T. Werfel
- Department of Dermatology and Allergy; Hannover Medical School; Hannover Germany
| | - K. Hoffmann-Sommergruber
- Department of Pathophysiology and Allergy Research; Medical University of Vienna; Vienna Austria
| | - G. Roberts
- David Hide Asthma and Allergy Research Centre; St Mary's Hospital; Newport Isle of Wight UK
- NIHR Southampton Respiratory Biomedical Research Unit; University of Southampton and University Hospital Southampton NHS Foundation Trust; Southampton UK
- Human Development and Health Academic Unit; Faculty of Medicine; University of Southampton; Southampton UK
| | - S. Halken
- Hans Christian Andersen Children's Hospital; Odense University Hospital; Odense Denmark
| | - L. Poulsen
- Laboratory of Medical Allergology; Allergy Clinic; Copenhagen University Hospital Gentofte; Hellerup Denmark
| | - R. van Ree
- Department of Experimental Immunology; Academic Medical Center; University of Amsterdam; Amsterdam the Netherlands
- Department of Otorhinolaryngology; Academic Medical Center; University of Amsterdam; Amsterdam the Netherlands
| | - B. J. Vlieg-Boerstra
- Department of Pediatric Respiratory Medicine and Allergy; Academic Medical Center; Emma Children's Hospital; Amsterdam the Netherlands
| | - A. Sheikh
- Allergy & Respiratory Research Group; Centre for Population Health Sciences; The University of Edinburgh; Edinburgh UK
- Division of General Internal Medicine and Primary Care; Brigham and Women's Hospital/Harvard Medical School; Boston MA USA
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Zakzuk J, Acevedo N, Cifuentes L, Bornacelly A, Sánchez J, Ahumada V, Ring J, Ollert M, Caraballo L. Early life IgE responses in children living in the tropics: a prospective analysis. Pediatr Allergy Immunol 2013; 24:788-97. [PMID: 24299508 DOI: 10.1111/pai.12161] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/06/2013] [Indexed: 11/26/2022]
Abstract
BACKGROUND There are few birth cohort studies analyzing IgE sensitization in the tropics. OBJECTIVES We aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with wheezing. METHODS Total and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1-S4) between 0 and 42 months. Parasite infection was evaluated by stool examination. RESULTS Maternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p = 0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08-0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around 3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B. tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00-2.28, p = 0.05). CONCLUSIONS In a socioeconomically deprived community from the tropics, sensitization to HDM allergens was very frequent at early life, especially to B. tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing.
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Affiliation(s)
- Josefina Zakzuk
- Institute for Immunological Research, University of Cartagena, Cartagena, Colombia; Foundation for the Development of Medical and Biological Sciences (Fundemeb), Cartagena, Colombia
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