title: The association between IgG4 antibodies to dietary factors, islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young.
abstract: BACKGROUND
  Infant dietary exposures have been linked to type 1 diabetes (T1D) development. IgG4 antibody responses to food antigens are associated with food intolerances but have not been explored prospectively in the period preceding T1D.
  
  
  METHODS
  Using a case-cohort design, IgG4 antibodies to ß-lactoglobulin, gluten, and ovalbumin were measured in plasma collected annually from 260 DAISY participants. Of those, 77 developed islet autoimmunity (IA), defined as positive for either insulin, GAD65 or IA-2 autoantibodies on two consecutive visits, and 22 developed T1D.
  
  
  RESULTS
  In mixed model analysis adjusting for HLA-DR status, T1D family history, age and ethnicity, higher ß-lactoglobulin IgG4 concentrations were associated with shorter breastfeeding duration (beta = -0.03, 95% Confidence Interval: -0.05, -0.006) and earlier first cow's milk exposure (beta = -0.04, 95% Confidence Interval: -0.08, 0.00). Higher gluten IgG4 was associated with older age at gluten introduction (beta = 0.06, 95% Confidence Interval: 0.00, 0.13). In proportional hazards analysis adjusting for HLA-DR status, T1D family history and ethnicity, IgG4 against individual or multiple dietary antigens throughout childhood were not associated with IA. In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D. Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92).
  
  
  CONCLUSIONS
  We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D. The association between higher ovalbumin and progression to T1D in children with IA should be explored in other populations.
authors.affiliation: Colorado School of Public Health, University of Colorado, Aurora, Colorado, United States of America.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Lamb
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Simpson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Seifert
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Scott
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
mesh_terms: D015551:Autoimmunity; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000276:immunology*; D004032:Diet; D004044:Dietary Proteins / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007223:Infant; D007515:Islets of Langerhans / Q000276:immunology*; D011379:Prognosis
chemical_list: D004044:Dietary Proteins; D007074:Immunoglobulin G