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

<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*^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. <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

Different Gm allotype amounts in human intravenous immunoglobulin (IVIG) preparations; survival of foreign Gm allotypes in immunodeficient patients

IVIG is used as standard replacement therapy in primary antibody deficiency. IVIG consists mainly of IgG. IVIG preparations were investigated with respect to Gm allotypes, which are characterized by various amino acid epitopes in the constant heavy chains of the IgG subclasses IgG1, IgG2 and IgG3. The alternative allelic Gm allotypes G1m(a) and G1m(f) of IgG1, G2m(n) and G2m(”) of IgG2 and G3m(g) and G3m(b) of IgG3 were measured by sensitive competitive ELISAs for G1m(a), G1m(f), G2m(n) and G3m(b). IgG subclass levels were quantified by radioimmunodiffusion (RID). Gm allotype quantities differed significantly in various IVIG products, with different products having half or double the amount of the different Gm allotypes. The results show the effect of the different manufacturing processes, but also indicate different physicochemical properties of Gm allotypes within the same IgG subclass. The different contents of Gm allotypes might be one reason for the variable levels of specific antibodies found in IVIG products. Immunodeficient patients with homozygous expression of Gm allotypes from IGHCG1, IGHCG2 and IGHCG3 were tested after infusion of foreign Gm allotypes. A prolonged survival was found for the G2m allotype, G2m(n), compared with G1m allotypes. Different half-lives were found for the alternative G1m(a) and G1m(f) allotypes, within the same IgG1 subclass

Aberrant IgG2 antibody response to Neisseria Meningitidis polysaccharide A after vaccination in frequently infected compared to healthy IgA-deficient individuals

In search for a possible explanation of the phenotypic heterogeneity in selective immunoglobulin (Ig)A deficiency, we studied the IgG2 antibody response to meningococcal polysaccharide A (PSA) in IgA-deficient (IgAd) individuals after vaccination with meningococcal A + C polysaccharide vaccine. Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as healthy controls, were studied. In response to meningococcal A + C polysaccharide vaccine, a significant titre increase of specific IgG2 anti-PSA was found in 71% of the control individuals, in 50% of the healthy and in 42% of the infection-prone IgAd individuals. The specific IgG2 response against meningococcal PSA was significantly lower in the infection-prone IgAd individuals compared to the controls (P < 0.05). Among the IgAd individuals who responded with a significant IgG2 antibody increase, the IgG2 antibody response was significantly lower in the infection-prone than in the healthy IgAd individuals (P < 0.05). Thus, a limited capacity to mount a specific IgG2 response may suggest a more profound antibody maturation defect in infection-prone IgAd patients compared to healthy IgAd individuals