biostudies-literatureMaillard NNIDDK NIH HHSNIGMS NIH HHS1503-12https://www.ebi.ac.uk/biostudies/studies/S-EPMC4483595biostudies-literatureUnknown26(7)Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan-binding lectin-associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome-wide association studies identified deletion of complement factor H-related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1-containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease.Journal of the American Society of Nephrology : JASNCurrent Understanding of the Role of Complement in IgA Nephropathy.PMC4483595R01 GM098539R01 DK082753DK078244K23 DK090207R01 DK078244DK082753GM098539DK090207R56 DK078244Fremeaux-Bacchi VJulian BAMaillard NNovak JKiryluk KGharavi AWyatt RJfalseCurrent Understanding of the Role of Complement in IgA Nephropathy.Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan-binding lectin-associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome-wide association studies identified deletion of complement factor H-related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1-containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease.2015-01-01T00:00:00Z2015 Jul2025-04-19T03:44:22.776Z2019-03-27T01:54:09ZS-EPMC44835952569446810.1681/ASN.201410100010.1681/asn.2014101000