Immunoglobulin heavy constant gamma (IGHG) (IgG heavy chain)

Human immunoglobulin G (IgG) heavy chains, also known as gamma chains, are the primary structural components of IgG antibodies, which constitute approximately 75% of serum immunoglobulins in humans [1][2]. These heavy chains consist of one variable (VH) domain for antigen recognition and three constant (CH1, CH2, CH3) domains that determine the antibody's isotype and effector functions [2][3]. The Fc region, formed by the CH2 and CH3 domains, is responsible for binding to Fc receptors (FcγRs) on effector cells and the neonatal Fc receptor (FcRn), which regulates IgG half-life by preventing lysosomal degradation [3][4]. In various autoimmune disorders, IgG heavy chains are components of pathogenic autoantibodies that mediate tissue destruction through complement activation or cellular cytotoxicity [4][5]. Therapeutic targeting of IgG heavy chains includes the use of enzymes like imlifidase to cleave the hinge region, or FcRn inhibitors like efgartigimod to accelerate the clearance of circulating IgG [5][6]. Monitoring serum IgG levels is essential during these treatments to manage the risk of secondary immunodeficiency and opportunistic infections [1][6].

Other names

Human immunoglobulin G heavy chainGamma chainIGHG1IGHG2IGHG3IGHG4IgG Fc region

Direct proteolytic cleavage of the IgG hinge region or competitive inhibition of the neonatal Fc receptor (FcRn) to prevent IgG recycling and accelerate its catabolism.