title: Exposure to a farming environment has allergen-specific protective effects on TH2-dependent isotype switching in response to common inhalants.
abstract: BACKGROUND
  IgE synthesis by human B cells results from allergen-dependent, T(H)2-mediated isotype switching. Exposure to a farming environment protects against IgE responses.
  
  
  OBJECTIVE
  We reconstructed allergen-dependent switching patterns in vivo to identify the level or levels at which farm exposure acts to protect against atopy.
  
  
  METHODS
  Serum IgG1 to IgG4 and IgE to grass (rPhl p 1 and rPhl p 5), cat (rFel d 1), and mite (rDer p 2) were assessed by means of ELISA in the Allergy and Endotoxin study population (812 children). Farm exposure was defined as currently living on a farm, exposure to stables/farm milk in the first year of life, or both.
  
  
  RESULTS
  Farm exposure did not affect allergen-specific IgG2 and IgG3 levels but had complex allergen-specific effects on IgG1, IgG4, and IgE levels. Exposure protected against grass-specific responses at every step along the IgG1/IgG4/IgE switching pathway but had no significant effect on mite responses. Protection from cat responses was concentrated at the IgG1 level. For all allergens, failure to express IgG1 was associated with low prevalence of IgG4 or IgE responses. Notably, coexpression of IgG1, IgG4, and IgE to grass was associated with increased risk of allergic disease and higher IgE levels compared with production of IgG1 and IgE without IgG4, suggesting IgG4 coexpression marks stronger activation of T(H)2-dependent events.
  
  
  CONCLUSIONS
  The protective effects of farm exposure were confined to T(H)2-dependent IgG1, IgG4, and IgE expression and were allergen and switch stage specific, suggesting that distinct mechanisms regulate individual steps within allergen-induced class switching in vivo.
  
  
  CONCLUSIONS
  Environmental interventions to prevent IgE expression might need to be tailored to specific allergens.
authors.affiliation: Functional Genomics Laboratory, Arizona Respiratory Center, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Stern
authors.forename: Josef
authors.initials: J
authors.lastname: Riedler
authors.forename: Dennis
authors.initials: D
authors.lastname: Nowak
authors.forename: Charlotte
authors.initials: C
authors.lastname: Braun-Fahrlander
authors.forename: Ines
authors.initials: I
authors.lastname: Swoboda
authors.forename: Nadja
authors.initials: N
authors.lastname: Balic
authors.forename: Kuan-Wei
authors.initials: KW
authors.lastname: Chen
authors.forename: Susanne
authors.initials: S
authors.lastname: Vrtala
authors.forename: Hans
authors.initials: H
authors.lastname: Grönlund
authors.forename: Marianne
authors.initials: M
authors.lastname: van Hage
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.forename: Susanne
authors.initials: S
authors.lastname: Spitzauer
authors.forename: Erika
authors.initials: E
authors.lastname: Von Mutius
authors.forename: Donata
authors.initials: D
authors.lastname: Vercelli
mesh_terms: D000383:Agriculture; D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D019570:Inhalation Exposure; D008297:Male; D006109:Poaceae / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; D006023:Glycoproteins; D007074:Immunoglobulin G; D007073:Immunoglobulin E; C059296:Fel d 1 protein, Felis domesticus