title: Human leukocyte antigen (DR1)-DQB1*0501 and (DR15)-DQB1*0602 haplotypes are associated with humoral responses to early food allergens in children.
abstract: BACKGROUND
  Infants' immunological responses to cow's milk (CM) proteins, which in 2-3% result in allergy, may partially depend on genetic factors. We evaluated whether genes with immunological functions, i.e. human leukocyte antigen (HLA) II, the protein tyrosine phosphatase, non-receptor type 22 (PTPN22) and filaggrin, modulate immune responses to dietary antigens.
  
  
  METHODS
  We analyzed 14 HLA class II haplotypes, the PTPN22 1858 SNP (R620W allele) and 5 known filaggrin null mutations from blood samples of 87 patients with CM allergy (CMA) and 76 control subjects (age 8.0-9.3 years). Serum levels of IgA, IgG, IgG1 and IgG4 antibodies to beta-lactoglobulin, alpha-casein and ovalbumin were measured with enzyme-linked immunosorbent assay, levels of IgE antibodies to CM, ovalbumin and birch with UniCap (Phadia, Uppsala, Sweden).
  
  
  RESULTS
  In children with CMA, the HLA (DR15)-DQB1*0602 haplotype was associated with high levels of beta-lactoglobulin-specific total IgG (p < 0.001) and IgG4 (p < 0.001) and alpha-casein-specific total IgG (p = 0.003) and IgG4 (p = 0.002), but not among control subjects. (DR1/10)-DQB1*0501 was associated with lower levels of beta-lactoglobulin-specific total IgG (p < 0.001) and IgG4 (p < 0.001), ovalbumin-specific total IgG (p = 0.002) and IgG4 (p < 0.001), particularly in control subjects (p < 0.001). Six children with eczema (3 with CMA) had the filaggrin mutation del22824. PTPN22 was not associated with specific antibody responses or CMA.
  
  
  CONCLUSIONS
  The HLA II, but not PTPN22 or filaggrin, genotype modulates humoral responses to early food allergens, whereas none of these genes was associated with CMA.
authors.affiliation: Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. erkki.savilahti@hus.fi
authors.forename: Emma M
authors.initials: EM
authors.lastname: Savilahti
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Minna
authors.initials: M
authors.lastname: Kiviniemi
authors.forename: Kristiina M
authors.initials: KM
authors.lastname: Saarinen
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Erkki
authors.initials: E
authors.lastname: Savilahti
mesh_terms: D000818:Animals; D029662:Betula / Q000276:immunology; D002364:Caseins / Q000276:immunology; D002417:Cattle; D002645:Chickens; D002648:Child; D003876:Dermatitis, Atopic / Q000235:genetics; D000091344:Filaggrin Proteins; D005387:Finland; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006239:Haplotypes / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics* / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007381:Intermediate Filament Proteins / Q000235:genetics; D007782:Lactoglobulins / Q000276:immunology; D016269:Milk Hypersensitivity / Q000235:genetics* / Q000276:immunology; D008894:Milk Proteins / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011058:Pollen / Q000276:immunology; D011110:Polymorphism, Genetic / Q000276:immunology; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics
chemical_list: D002364:Caseins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007381:Intermediate Filament Proteins; D007782:Lactoglobulins; D008894:Milk Proteins; D007073:Immunoglobulin E; D010047:Ovalbumin; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22