Immunoglobulin GM (γ marker) allotypes and their role in immune response and disease susceptibility

Immunoglobulin GM (γ marker) allotypes are encoded by 3 very closely linked and highly homologous immunoglobulin heavy chain G (IGHG) genes-IGHG1, IGHG2, and IGHG3-on chromosome 14q32. They are localized on the constant region of γ1, γ2, and γ3 chains. There are currently 18 serologically testable GM specificities. Linkage disequilibrium in the GM system within a racial/ethnic group is almost absolute and the determinants are transmitted as haplotypes. Major racial/ethnic groups are characterized by unique arrays of several GM haplotypes. In this article, I review the basic genetics of GM allotypes, their role in antibody responses to infectious pathogens and vaccines, their contribution to Fc-mediated effector functions, and their potential role in immunotherapy. Additionally, I discuss the association of GM allotypes with many autoimmune, infectious, and malignant diseases.