Innate IgG Molecules and Innate B Cells Expressed by Immunoglobulin Constant Heavy G Chain (Fcγ) Genetic Marker Genes Are Involved in the ‘Allergic March' of IgE Sensitization in Children

Background: Interindividual variations of immunoglobulin constant heavy G chain (IGHG) genes on chromosome 14q32.3 are identified by alternative genetic markers (GM) of IgG3, IgG1 and IgG2, respectively. They express structurally and functionally innate IgG molecules and B cells, associated with allergic disease, replicated in several studies. Materials and Methods: 1-year-old and 10-year-old, IgE-sensitized and non-sensitized children from the German Multicenter Allergy Study birth cohort were assessed by new serological methods for the mendelian IGHG (Fcγ) (GM) genes, as innate IgG molecules and innate B cells. Results: Food allergy sensitization in thirty-five 1-year-old children (124 not sensitized) was associated with the IGHG*bfn haplotype and B*bfn cells (OR 1.9, 95% CI 1.2-3.1; p = 0.010). Aeroallergen sensitization in ninety-nine 10-year-old children (95 not sensitized) was associated with the same genes (OR 1.4, 95% CI 1.02-1.9; p = 0.034). The IgE sensitization was most prominent in the restrictive homozygous IGHG*bfn/*bfn diplotype, 34% at age 1, increasing to 60% at age 10, rating the highest numbers of positive IgE tests, expressing increased levels of IgE and innate IgG2*n. Conclusions: The IGHG*bfn haplotype (B*bfn cells) and increased innate IgG2*n levels are predictive factors for IgE sensitization in childhood. IGHG genes can be assessed for prognostic and preventive purposes in clinical care.