Pathogenic role of IgA receptors in IgA nephropathy

Abstract

The pathogenesis of IgA nephropathy (IgAN) involves the deposition of aberrant glycosylated IgA1 and/or of IgA1-immune complexes (IC) in the glomerular mesangium. The mechanisms involved in the generation of IgA1-IC and how they are deposited in the mesangium are just emerging. We propose a model whereby two types of IgA receptors participate in sequential steps to promote the development of IgAN, with soluble FcalphaRI (CD89) being initially involved in the formation and/or amplification of the size of circulating IgAIC and, subsequently, transferrin receptor (CD71), in mediating mesangial deposition of nephritogenic IgA1-IC. Activation of transmembrane FcalphaRI associated with FcRgamma adaptor following interaction with IgA-IC is involved in aggravation of IgAN through induction of leukocyte infiltration. Taken together, understanding of the role of IgA receptors in physiology and physiopathology will open new avenues for therapeutic strategies in IgAN.