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“Default” versus “pre-atopic” IgG responses to foodborne and airborne pathogenesis-related group 10 protein molecules in birch-sensitized and nonatopic children - 11/05/15

Doi : 10.1016/j.jaci.2014.09.048 
Stephanie Hofmaier a, Laura Hatzler, MD a, Alexander Rohrbach a, Valentina Panetta, MSc b, Dani Hakimeh, MD a, Carl Peter Bauer, MD c, Ute Hoffman, MD c, Johannes Forster, MD d, Fred Zepp, MD e, Antje Schuster, MD f, Philippe Stock, MD a, Ulrich Wahn, MD a, Thomas Keil, MD g, h, Susanne Lau, MD a, Paolo Maria Matricardi, MD a,
a Department of Paediatric Pneumology & Immunology, Charité–Universitätsmedizin Berlin, Berlin, Germany 
b L'altrastatistica srl, Consultancy & Training, Biostatistics Office, Rome, Italy 
c Department of Pediatrics, Technical University of Munich, Munich, Germany 
d Department of Pediatrics St Hedwig, St Josefs Hospital, Freiburg, Germany 
e Department of Pediatrics and Adolescent Medicine, Johannes Gutenberg University Medical Centre, Mainz, Germany 
f Department of Pediatric Cardiology and Pneumology, Heinrich-Heine-University, Düsseldorf, Germany 
g Institute of Social Medicine, Epidemiology and Health Economics, Charité–Universitätsmedizin Berlin, Berlin, Germany 
h Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany 

Corresponding author: Paolo Maria Matricardi, MD, Department of Paediatric Pneumology and Immunology, Charité Medical University, Augustenburger Platz, 1, 13353 Berlin, Germany.

Abstract

Background

The route and dose of exposure are believed to be relevant factors in the sensitization process. Pathogenesis-related group 10 protein (PR-10) molecules are a family of allergenic proteins shared by many pollens (eg, birch and alder) and foods (eg, apple, peach, and soy). Children are exposed to both pollen-derived (inhaled) and food-derived (ingested) PR-10 molecules.

Objective

We sought to investigate the role of route and dose of exposure in the evolution of IgG and IgE responses to recombinant PR-10 molecules.

Methods

The German Multicentre Allergy Study examined a birth cohort born in 1990. Blood samples were collected at the ages of 1, 2, 3, 5, 6, 7, 10, and 13 years. Participants were included in the present analysis if they had (1) at least 1 serum sample at each of the 4 age periods or time points (1-3 years, 5-7 years, 10 years, and 13 years) and (2) IgE responses to birch (children with birch atopy) or no IgE response at all to 9 common aeroallergens and food allergens (nonatopic children). Therefore serum IgE antibodies to a panel of 4 airborne and 5 foodborne extracts, as well as to Bet v 1, were measured in singleplex assays, whereas IgG and IgE antibodies to a panel of 3 airborne PR-10 molecules (rBet v 1, rAln g 1, and rCor a 1.0101) and 7 foodborne PR-10 molecules (rCor a 1.0401, rMal d 1, rPru p 1, rGly m 4, rAra h 8, rApi g 1, and rDau c 1) were tested by using a multiplex microarray.

Results

In the present analyses we included 28 children with birch atopy and randomly selected 28 nonatopic children from the 190 children fulfilling the inclusion criteria. Two different patterns of IgG responses to PR-10 molecules were identified. Among nonatopic subjects, a “default” IgG response was directed mostly against foodborne PR-10, started often before age 2 years, stayed weak, and was mostly transient. Among all atopic subjects, the default IgG response at age 1 year was overwhelmed after age 2 years by an “pre-atopic” IgG response, which started with or shortly before the IgE response and was intense and persistent. This atopic IgG response, as well as the IgE response, involved progressively more foodborne PR-10 proteins with frequencies and levels related to their homology with Bet v 1.

Conclusions

The results suggest that children have a default antibody response to PR-10 molecules, which is early, weak, and transient; does not involve IgE; and is initiated by foodborne PR-10. By contrast, an atopic antibody response to PR-10 molecules is delayed, strong, and persistent; involves both IgG and IgE; and is initiated by airborne PR-10.

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Key words : Allergen, Bet v 1, birch pollen, birth cohort, childhood, IgE, IgG, pathogenesis-related group 10 protein

Abbreviations used : ISU, MAS, PR-10, SPHIA


Plan


 The present analysis was supported by the German Research Foundation (DFG), grant number MA-4740/1-1. The German Multicentre Allergy Study (MAS) birth cohort was funded further by grants from the German Federal Ministry of Education and Research (07015633, 07 ALE 27, 01EE9405/5, and 01EE9406) and the German Research Foundation (KE 1462/2-1).
 Disclosure of potential conflict of interest: This study was funded by the German Research Foundation (DFG), grant number MA-4740/1-1. The MAS birth cohort was funded further by grants from the German Federal Ministry of Education and Research (07015633, 07 ALE 27, 01EE9405/5, 01EE9406) and the German Research Foundation (KE 1462/2-1). A. Schuster receives consultancy fees from HAL Allergy, and has received payment for delivering lectures from GlaxoSmithKline, Merck, Forest Labs, Thermo Fisher Scientific, Roche, Novartis, ALK-Abelló, Grünenthal, Asche-Chiesi, and HAL Allergy. T. Keil is employed by Charité Berlin and has received or has grants pending from the European Union (MeDALL-EU FP7 grant no. 261357, iFAAM-EU FP7 grant no. 312147, MAS - DFG grant no. KE 1462/2-1). The rest of the authors declare that they have no relevant conflicts of interest.


© 2014  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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