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 β-lactoglobulin, α-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 β-lactoglobulin-specific total IgG (p < 0.001) and IgG4 (p < 0.001) and α-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 β-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.