Supplementary Material for: From Genotypes of Immunoglobulin Constant Heavy G Chains (Fcγ) (GM) Genes <b><i>(IGHG)</i></b> to Phenotypes in Childhood Asthma

2012-05-04T00:00:00Z (GMT) by Oxelius V.-A.
<b><i>Background:</i></b> IgE-mediated allergy is associated with immunoglobulin heavy constant G chain (Fcγ) (GM) genes <i>(IGHG)</i> 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. <b><i>Objective:</i></b> To investigate different <i>IGHG</i> (GM) gene complexes in a childhood asthma population for allergy parameters. <b><i>Methods:</i></b><i>IGHG</i> 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 <i>IGHG</i> 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. <b><i>Results:</i></b> The group with homozygous <i>IGHG</i>*<i>bfn/</i>*<i>bfn</i> (B1/B1 cells) demonstrated low IgG1*f levels (p < 0.001) but increased IgG2*n levels (p < 0.001) together with increasd IgE and <i>IGHG2</i>*<i>n </i>gene dose-dependent IgE sensitization (atopic phenotype). The <i>IGHG</i>*<i>bf–n</i>/*<i>bf–n</i> (B2/B2 cells) demonstrated low IgG1*f (p < 0.05) and IgG2*–n (p < 0.001) and the <i>IGHG</i>*<i>ga–n/</i>*<i>ga–n</i> (B4/B4 cells) low IgG1*a (p < 0.001) and IgG2*–n (p < 0.02) together with low IgE sensitization (non-atopic phenotype). B*<sup>bfn</sup> (B1) and B*<sup>bf–n</sup> (B2) demonstrated increased numbers of peripheral blood eosinophils, compared to B*<sup>gan</sup> (B4) cells, which demonstrated increased peripheral blood CD8 lymphocytes instead. <b><i>Conclusion:</i></b><i>IGHG</i> diplotypes present different phenotypes in childhood asthma. The <i>IGHG2</i>*n dose relationship to IgE sensitization and increased IgG2*n levels in IgE sensitized are risk markers for IgE-mediated asthma. The opposite <i>IGHG2</i>*<i>–n</i> presents non-IgE-mediated asthma and IgG subclass deficiencies.