Immunoglobulin constant heavy G subclass chain genes in asthma and allergy

Abstract

The IGHG (ImmunoGlobulin constant Heavy G chain) genes are situated close to the IGHE gene on chromosome 14q32, 5'mu, delta, gamma3, gamma1, alpha1, gamma2, gamma4, epsilon, alpha2, 3', in linkage disequilibrium. The polymorphism of gamma3, gamma1 and gamma2 genes, is investigated as alternative allotypes. They are inherited in a Mendelian fashion and are expressed randomly in allelic exclusion. The alternative and functionally different gamma3, gamma1 and gamma2 gene variants, are found in four IGHG haplotypes, coding 4 B-cell variants: IGHG*bfn (=B1-cells), IGHG*bf-n (=B2-cells), IGHG*gan (=B3-cells) and IGHG*ga-n (=B4-cells). The dominance of the IGHG2*n allele from the IGHG*bfn haplotype (=B1-cells) has been shown in repeated investigations, namely in patients with asthma and allergy with increased serum levels of IgE > 600 ku/l and more often so in those with IgE > 1,000 ku/l or IgG4>1 g/l, in childhood asthma patients with mean level of IgE = 1,762 ku/l and in allergen exposed individuals developing laboratory animal allergy. In children with non-atopy and mean IgE level = 9.5 ku/l there is instead a dominance of the alternative allotypes from the IGHG*ga-n (=B4-cells) with IGHG2*-n alleles. In a case-control study allergic children with a family history of allergy, clinically manifest allergy and/or positive SPT, the IGHG*bfn haplotype (=B1-cells) with the IGHG2*n allele dominates, with increased risk of atopy and the IGHG*bf-n haplotype (=B2-cells) with the IGHG2*-n allele is infrequent with low risk, probably protective against atopy. The phenotypic expressions of the IGHG*bfn haplotype (=B1 cells) and IGHG*bfn/*bfn diplotypes (B1/B1-cells) are increased IgG2*n allotype together with increased IgE serum levels and IgE sensitisation in agreement with atopy. The alternative IGHG*ga-n/*ga-n diplotype (B4/B4-cells) express low IgG1*a- and IgG2*-n allotypes, together with low IgE and non-IgE sensitisation, in agreement with non-atopy. Together these studies have given us a greater understanding of the involvement of IGHG genes, IGHG coded B-cells and immunochemical and functional variants of IgG molecules describing different forms of asthma and allergy, which will improve diagnoses and treatment.