IgA receptors in health and disease

Abstract

The varied interaction of the Fc region of IgA with receptors confers this antibody class with many of its unique properties. The epithelial polymeric Ig receptor on mucosal epithelial cells transports polymeric immunoglobulin A (pIgA) produced by mucosal B cells to the mucosal surface where, in complex with the secretory component (SC), this secretory immunoglobulin A (SIgA) excludes the multitude of dietary, environmental, and microbial antigens that continuously bombard the mucosae. In health, this IgA-mediated exclusion not only forms the initial defence against infection, it also spares the systemic immune system from potentially deleterious responses to innocuous antigens which can otherwise culminate in inflammatory bowel disease or asthma. Beyond antigen exclusion, in closer encounters with antigens, IgA receptors play roles in protective immunity and disease. FcaRI is the principal myeloid IgA receptor and is responsible for differing IgA-mediated effector responses such as respiratory burst, degranulation, and phagocytosis variously by granulyoctes, monocytes, and macrophages. Furthermore an unknown IgA receptor specific for the secretory component (SC) elicits powerful effector responses from eosinophils. On dendritic cells, FcaRI participates in antigen presentation while on microfold cells, key cells in mucosal antigen presentation, another unknown IgA receptor functions in the transport of antigens across the mucosal epithelial barrier. The activity of another uncharacterized IgA1/IgD receptor on T cells may affect autoimmune disorders. The interplay of different IgA receptors affects immune complex deposition in the common renal disease immunoglobulin A nephropathy (IgAN). Finally, the therapeutic application of various IgA receptors has been sought in the areas of infectious disease, vaccines, and cancer.