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J Am Soc Nephrol. 2015 Jul;26(7):1503-12. doi: 10.1681/ASN.2014101000. Epub 2015 Feb 18.

Current Understanding of the Role of Complement in IgA Nephropathy.

Author information

1
University of Alabama at Birmingham, Departments of Microbiology and Medicine, Birmingham, Alabama; Université Jean Monnet, Groupe sur l'immunité des Muqueuses et Agents Pathogènes, St. Etienne, Pôle de Recherche et d'Enseignement Supérieur, Université de Lyon, Lyon, France;
2
University of Tennessee Health Science Center and Children's Foundation Research at the Le Bonheur Children's Hospital, Memphis, Tennessee;
3
University of Alabama at Birmingham, Departments of Microbiology and Medicine, Birmingham, Alabama;
4
Columbia University, Department of Medicine, New York, New York; and.
5
Unité Mixte de Recherche en Santé 1138, Team "Complement and Diseases," Cordeliers Research Center, Paris, France.
6
University of Alabama at Birmingham, Departments of Microbiology and Medicine, Birmingham, Alabama; jannovak@uab.edu.

Abstract

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.

KEYWORDS:

IgA nephropathy; complement; immune complexes

PMID:
25694468
PMCID:
PMC4483595
DOI:
10.1681/ASN.2014101000
[Indexed for MEDLINE]
Free PMC Article

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