From Genotypes of Immunoglobulin Constant Heavy G Chains (Fcγ) (GM) Genes (IGHG) to Phenotypes in Childhood Asthma

Abstract

Background: IgE-mediated allergy is associated with immunoglobulin heavy constant G chain (Fcγ) (GM) genes (IGHG) on chromosome 14q32.3. Investigation of the alternative GM allotypes of γ3, γ1 and γ2 chains has disclosed new structural and functional IgG subclasses and B-cell variants, with possible effects on childhood asthma. Objective: To investigate different IGHG (GM) gene complexes in a childhood asthma population for allergy parameters. Methods:IGHG alleles and correlated allotypic (allelic) IgG subclass levels were analyzed with a sensitive indirect competitive ELISA in 10-year-old children with bronchial asthma. Individual IGHG diplotype-, genotype- and haplotype-related B cells were compared for allelic IgG subclass levels, IgE sensitization, IgE, IgA and IgM levels, and numbers of peripheral blood eosinophils and lymphocytes. Results: The group with homozygous IGHG*bfn/*bfn (B1/B1 cells) demonstrated low IgG1*f levels (p < 0.001) but increased IgG2*n levels (p < 0.001) together with increasd IgE and IGHG2*n gene dose-dependent IgE sensitization (atopic phenotype). The IGHG*bf–n/*bf–n (B2/B2 cells) demonstrated low IgG1*f (p < 0.05) and IgG2*–n (p < 0.001) and the IGHG*ga–n/*ga–n (B4/B4 cells) low IgG1*a (p < 0.001) and IgG2*–n (p < 0.02) together with low IgE sensitization (non-atopic phenotype). B*^bfn (B1) and B*^bf–n (B2) demonstrated increased numbers of peripheral blood eosinophils, compared to B*^gan (B4) cells, which demonstrated increased peripheral blood CD8 lymphocytes instead. Conclusion:IGHG diplotypes present different phenotypes in childhood asthma. The IGHG2*n dose relationship to IgE sensitization and increased IgG2*n levels in IgE sensitized are risk markers for IgE-mediated asthma. The opposite IGHG2*–n presents non-IgE-mediated asthma and IgG subclass deficiencies.