Immunopathogenetic aspects of IgA nephropathy.

IgA nephropathy is the most common primary glomerulonephritis worldwide, and is an important cause of end-stage renal failure. The pathogenesis of the disease has unfortunately remained unclear despite a considerable research effort in the past twenty years. Combining data from the recent literature with our own findings we propose a pathogenetic model in which a selective IgA1 hyperresponsiveness plays a key role. Everyday infections lead to abnormally high plasma IgA1 immune responses in patients, with the bone marrow as the main production site of this increased circulating IgA1. However, may questions still remain unanswered, such as: why are patients hyperresponsive with respect to plasma IgA1? Which antigens are involved? What causes the mesangial deposition of IgA1, and the subsequent tissue damage?