IgA Nephropathy: Pathogenesis of the Most Common Form of Glomerulonephritis

Abstract

IgA nephropathy (IgAN) is being recognized increasingly as a common form of glomerulonephritis with progressive potential (17, 29, 42). Our initial goal here is briefly to consider the definition, clinical features, and major clinical problems of IgAN, and the special characteristics of the secretory immune system, the major source of IgA in the body. Then follows a critical discussion of experimental and clinical observations which provide a conceptual framework for a scheme of pathogenesis based on distinctive features of immunity in mucous membranes and altered regulation of mucosal immune responses due to a defect in mucosal IgG/IgM tolerogenesis. We believe that, in the main, IgAN is an immune complex disease resulting from a poorly controlled mucosal immune response to environmental antigens to which the host is chronically subject. The deposited IgA is likely antibody to viral or dietary antigen. Evidence exists for other mechanisms, which we consider less likely.