IgA1

IgA1 is one of the two subclasses of immunoglobulin A (IgA) found in humans, the other being IgA2. In the bloodstream, IgA1 is the predominant form, comprising the majority of serum IgA, while IgA2 is more common in some mucosal secretions. A distinguishing feature of IgA1 is its relatively long hinge region, about 13 amino acids, which provides flexibility for antigen binding but makes the molecule more susceptible to proteolysis by bacterial IgA proteases. IgA2 has a shorter hinge and greater protease resistance.

IgA1 is produced by plasma cells in mucosa-associated lymphoid tissue and bone marrow. It is secreted into serum as monomeric IgA1 and into mucosal secretions as dimeric or polymeric IgA, bound to a J chain and transported across epithelial cells by the polymeric Ig receptor, which adds the secretory component to form secretory IgA. This secretory form is optimized for luminal defense in mucosal surfaces.

Functionally, IgA1 participates in immune exclusion by neutralizing pathogens and preventing their adherence to mucosal surfaces, thereby limiting infection. It interacts with Fc alpha receptors (CD89) on various myeloid cells to mediate effector responses such as phagocytosis and inflammatory signaling, though secretory IgA in mucosa tends to promote non-inflammatory protection.

Clinical relevance includes selective IgA deficiency, the most common primary immunoglobulin deficiency. IgA1 abnormalities, particularly galactose-deficient IgA1, are implicated in IgA nephropathy, where immune complexes deposit in the kidneys.