title: "Default" versus "pre-atopic" IgG responses to foodborne and airborne pathogenesis-related group 10 protein molecules in birch-sensitized and nonatopic children.
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.
authors.affiliation: Department of Paediatric Pneumology & Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hofmaier
authors.affiliation: Department of Paediatric Pneumology & Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Hatzler
authors.affiliation: Department of Paediatric Pneumology & Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rohrbach
authors.affiliation: L'altrastatistica srl, Consultancy & Training, Biostatistics Office, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Panetta
authors.affiliation: Department of Paediatric Pneumology & Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Dani
authors.initials: D
authors.lastname: Hakimeh
authors.affiliation: Department of Pediatrics, Technical University of Munich, Munich, Germany.
authors.forename: Carl Peter
authors.initials: CP
authors.lastname: Bauer
authors.affiliation: Department of Pediatrics, Technical University of Munich, Munich, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hoffman
authors.affiliation: Department of Pediatrics St Hedwig, St Josefs Hospital, Freiburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Forster
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Johannes Gutenberg University Medical Centre, Mainz, Germany.
authors.forename: Fred
authors.initials: F
authors.lastname: Zepp
authors.affiliation: Department of Pediatric Cardiology and Pneumology, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Schuster
authors.affiliation: Department of Paediatric Pneumology & Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Stock
authors.affiliation: Department of Paediatric Pneumology & Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wahn
authors.affiliation: Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Berlin, Germany; Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Keil
authors.affiliation: Department of Paediatric Pneumology & Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lau
authors.affiliation: Department of Paediatric Pneumology & Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address: paolo.matricardi@charite.de.
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Matricardi
mesh_terms: D000293:Adolescent; D000485:Allergens / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005512:Food Hypersensitivity / Q000453:epidemiology / Q000276:immunology*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010940:Plant Proteins / Q000276:immunology*; D011446:Prospective Studies; D006255:Rhinitis, Allergic, Seasonal / Q000453:epidemiology / Q000276:immunology*; D016036:Seroepidemiologic Studies
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D010940:Plant Proteins; D007073:Immunoglobulin E
keywords: Allergen; Bet v 1; IgE; IgG; birch pollen; birth cohort; childhood; pathogenesis-related group 10 protein