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.