关键词: IgA肾病, 补体, 发病机制, 生物标志物

Abstract:

Immunoglobulin A nephropathy (IgAN), an autoimmune disease mediated by pathogenic immune complexes consisting of galactosedeficient IgA1 bound by  antibodies, is characterized by the deposition of IgA in the mesangium of glomeruli. The mesangial IgA has been found to consist mainly of polymeric IgA1 which drives the activation of the mesangial cells and results in excessive production of several inflammatory mediators. The activation of mesangial cells is amplified by the ability of IgA to activate the complement system, mainly via the alternative pathway and lectin pathway. Properdin and factor H (FH) in the alternative pathway and mannanbinding lectin, mannanbinding lectinassociated serine proteases 1 and 2, and C4d in the lectin pathway are present in the mesangial immunodeposition. Protein products of complement factor Hrelated genes (CFHR) 1 and 3 impact inhibition of complement by FH, in the way of competing with FH in the regulation of the alternative pathway. Genomewide association studies identified deletion of CFHR1 and CFHR3 play a protective role in IgAN. Complement factors and fragments could serve as biomarkers of IgAN in serum, urine, and renal tissue, for IgAimmune complexes contribute to active complement system. Recently, several literatures reported patients with IgAN benefited from anticomplement therapy. However, the longtime effect still needs to be confirmed by clinical studies. In this review, we summarize the contribution of abnormal complement activation to IgAN.

Key words: IgA nephropathy, complement, pathogenesis, biomarker