The unexplored roles of human serum IgA

Abstract

The roles of human serum IgA, in contrast to that of mucosal IgA, are relatively unexplored. Previous studies have shown that IgA mediates either pro- or anti-inflammatory effects in innate immune cells. Serum IgA has been shown to interact with many proteins and glycoproteins of which the functions and mechanisms are not fully characterized. Here, we present fresh perspectives into the roles of serum IgA, describing novel IgA-protein interactions, the importance of its glycosylation status in normal functions, and the plausible role of IgA as a driver and regulator of autoimmune diseases/immune overactivation. Other potential roles, including the regulation of cytokines, effector cell function, and homeostasis, are considered in view of the maintenance of immune function. We anticipate future research to uncover new anti-inflammatory or pro-inflammatory roles of human serum IgA in immune functions and dysfunctions, with implications on systemic lupus erythematosus (SLE).

FIG. 1.

Roles of serum IgA. Structure of monomeric serum IgA1 is shown on the left. (a) Role of serum IgA in regulating immune complex formation and immune overactivation (Panda et al., 2013). (b) Serum IgA associates with serum proteins and cell surface receptors (through glycan chains present on various regions of the antibody) to effect various functions (Kerr, 1990). (c) Monovalent binding of FcαRI by monomeric serum IgA Fab transduces inhibitory signals that extend to other receptors, such as FcγR, FcɛRI, TLR4, CCR2, and TNFR, and affects the activation threshold of innate immune cells. Local concentrations of serum IgA in various tissues thus affect the cytokines released by innate immune cells and play a role in the shaping of the adaptive immunity (Dewey, ; Fearon and Locksley, ; Kanamaru et al., ; Pasquier et al., 2005). (d) Mature naive B cells that are activated in the gut may home into the marginal zone of the spleen, contributing IgA antibodies that are specific for gut pathogens/commensal antigens to the serum IgA pool. Gut-resident B cells further contribute to the serum IgA pool in the form dimeric IgA (Vossenkamper et al., ; Mestecky et al., 1999). Figure is not drawn to scale.