isotypesIgA

Immunoglobulin A (IgA) exists in two human isotypes, IgA1 and IgA2, collectively known as the IgA subclasses. They are the main antibodies of mucosal immunity, produced by plasma cells in mucosa-associated lymphoid tissue and other sites, and are present in secretions such as saliva and intestinal fluids as secretory IgA, as well as in serum in monomeric form.

IgA structure and distribution: IgA1 has a longer hinge region than IgA2, making it more susceptible to bacterial proteases; IgA2 has a shorter hinge and greater protease resistance. In serum, IgA is predominantly monomeric; in secretions, it is secretory IgA, typically a dimer joined by a J chain and associated with a secretory component derived from the polymeric Ig receptor (pIgR) during transcytosis across epithelial cells.

Function: Secretory IgA mediates immune exclusion at mucosal surfaces by neutralizing pathogens and toxins and preventing their adherence to epithelial cells, while limiting inflammatory responses. IgA can also engage Fc alpha receptors on certain leukocytes to trigger specific effector functions when needed.

Clinical relevance: Selective IgA deficiency is a common primary immunodeficiency characterized by low or absent IgA, with variable clinical impact. Many individuals are asymptomatic but may have increased susceptibility to mucosal infections and allergies. IgA nephropathy involves deposition of IgA1-containing immune complexes in the kidneys. IgA antibodies are also used in serologic testing for certain mucosal disorders.

Genetics: The constant regions of the IgA heavy chain are encoded by IGHA1 and IGHA2, located in the immunoglobulin heavy chain locus on chromosome 14 in humans.