Restricted immunoglobulin constant heavy G chain genes in primary immunodeficiencies

Some primary immunodeficiencies (PIDs) express low serum levels of antibodies. The constant heavy G chain (IGHG) genes, also representing Fc domains of γ3, γ1 and γ2 on chromosome 14q32.3, genotyped by the alternative IgG subclass allotypes, found in four fixed IGHG haplotypes, designating four B cell variants, were identified by a competitive ELISA and double immunodiffusion. IGHG genes were hypothesized to contribute to the development of PIDs. From 235 Caucasian patients, the homozygous IGHG⁎bf-n/⁎bf-n diplotype (B⁎bf-n/B⁎bf-n cells) dominated significantly in 43 IgG2 deficiency (OR 6.0), 32 common variable immunodeficiency (OR 4.6) and 22 Ataxia telangiectasia (OR 3.0) and the IGHG⁎ga-n/⁎ga-n diplotype (B⁎ga-n/B⁎ga-n cells) dominated in 53 IgG3 deficiency (OR 10.6) and 21 Wiscott–Aldrich syndrome (OR 4.1). 62 IgA deficiency patients were dominated by both diplotypes (OR 2.3 and OR 2.8 respectively). Restricted IGHG genes, restricted IgG allotypes (Fc domains) and restricted B cells are significant in PIDs for diagnosis, treatment and pathogenetic mechanisms.