IGHA1

IGHA1 is the gene that encodes the constant region of the alpha-1 heavy chain of immunoglobulin A (IgA1) in humans. It lies in the immunoglobulin heavy chain locus on chromosome 14, within the alpha heavy-chain constant region gene cluster, and together with IGHA2 defines the IgA1 isotype. The IGHA1 gene provides the Cα1 domain used in assembling IgA1 antibodies, which can be produced as monomers in serum or as polymeric IgA in mucosal secretions after joining with the J chain and transcytosis across epithelium via the polymeric Ig receptor to form secretory IgA.

IgA1 differs from other isotypes in its hinge region, which is longer than that of IgA2. This longer hinge grants IgA1 greater flexibility and antigen-binding versatility but also makes it more susceptible to cleavage by certain bacterial proteases. IgA1 antibodies exert their protective effects mainly at mucosal surfaces, neutralizing pathogens and toxins, and they participate in immune defense through interactions with Fc alpha receptors on myeloid cells (notably CD89). In secretions, polymeric IgA1 is transported as secretory IgA, which helps retain antibody activity in the harsh mucosal environment.

Clinical relevance includes selective IgA deficiency, the most common primary immunodeficiency, characterized by low or absent IgA with variable susceptibility to infections. Abnormalities in IgA1, such as galactose-deficient IgA1, are associated with IgA nephropathy due to immune complex formation and renal deposition. The IGHA1 gene is subject to class switch recombination during B-cell maturation, enabling production of IgA1 in response to appropriate cytokine signals, including TGF-β.