Roles of immunoglobulin GM and KM allotypes and Fcγ receptor 2 A genotypes in humoral immunity to a conserved microbial polysaccharide in pulmonary diseases.

Immunoglobulin GM (γ marker) and KM (κ marker) allotypes-encoded by immunoglobulin heavy chain G (IGHG) and immunoglobulin κ constant (IGKC) genes-have been shown to be associated with immune responsiveness to a variety of self and nonself antigens. The aim of the present investigation was to determine whether allelic variation at the GM and KM loci was associated with antibody responsiveness to poly-N-acetyl-D-glucosamine (PNAG), a broadly-conserved surface polysaccharide expressed by many microbial pathogens. In addition, we wished to determine whether Fcγ receptor 2 A (FCGR2A) genotypes, which have been shown to be risk factors for some pathogens, also influenced antibody responses to PNAG. DNA from 257 patients with various pulmonary diseases (PD) was genotyped for several GM, KM, and FCGR2A alleles, and plasma were characterized for anti-PNAG IgG antibodies. The levels of IgG4 antibodies to PNAG were associated with FCGR2A genotypes (p = 0.01). Also, KM and FCGR2A alleles epistatically contributed to anti-PNAG IgG3 antibody responses: subjects with KM 1/1 or KM 1/3 and homozygous for the R allele of FCGR2A had the highest levels of anti-PNAG IgG3 antibodies compared to all other genotype combinations. If confirmed by larger studies, these results are potentially relevant to immunotherapy against many PNAG-expressing infectious pathogens.