Human leukocyte antigen (DR1)-DQB1*0501 and (DR15)-DQB1*0602 haplotypes are associated with humoral responses to early food allergens in children

Int Arch Allergy Immunol. 2010;152(2):169-77. doi: 10.1159/000265538. Epub 2009 Dec 16.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Betula / immunology
  • Caseins / immunology
  • Cattle
  • Chickens
  • Child
  • Dermatitis, Atopic / genetics
  • Filaggrin Proteins
  • Finland
  • HLA-DQ Antigens / genetics*
  • HLA-DQ beta-Chains
  • Haplotypes / immunology*
  • Humans
  • Immunity, Humoral / genetics*
  • Immunity, Humoral / immunology
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Intermediate Filament Proteins / genetics
  • Lactoglobulins / immunology
  • Milk Hypersensitivity / genetics*
  • Milk Hypersensitivity / immunology
  • Milk Proteins / immunology
  • Ovalbumin / immunology
  • Pollen / immunology
  • Polymorphism, Genetic / immunology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics

Substances

  • Caseins
  • FLG protein, human
  • Filaggrin Proteins
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Immunoglobulin A
  • Immunoglobulin G
  • Intermediate Filament Proteins
  • Lactoglobulins
  • Milk Proteins
  • Immunoglobulin E
  • Ovalbumin
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22