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Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation

Lookup NU author(s): Professor Tim Goodship, Professor Claire Harris

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Abstract

C3 nephritic factors are autoantibodies that prolong the half-life or prevent regulation of the alternative pathway C3 convertase, resulting in uncontrolled complement activation. They are strongly associated with renal disease but their role in pathogenesis remains controversial. Here we optimized and compared a panel of assays to identify and interrogate nephritic factor activities. Of 101 patients with histologic or clinically evident disease, 48 were positive in some or all assays. In the presence of properdin, binding of autoantibody was detected in 39 samples and convertase stabilization was detected in 36. Forty-two of 48 nephritic factors tested prevented convertase decay by factor H, and most of these by decay accelerating factor (28) and complement receptor 1 (34). Representative properdin-independent nephritic factors had no effect on C5 cleavage and terminal pathway activity, while properdin-dependent nephritic factors enhanced activity. Biacore analysis of four purified IgG samples confirmed resistance to decay and showed that properdin-independent nephritic factors increased convertase half-life over 50-fold, whereas properdin-dependent nephritic factors increased the half-life 10- to 20-fold and also increased activity of the C3 convertase up to 10-fold. Thus, our study provides a rational approach to detect and characterize nephritic factors in patients. Kidney International (2012) 82, 1084-1092; doi:10.1038/ki.2012.250; published online 1 August 2012

Publication metadata

Author(s): Paixão-Cavalcante D, López-Trascasa M, Skattum L, Giclas PC, Goodship TH, Rodríguez de Córdoba S, Truedsson L, Morgan BP, Harris CL

Publication type: Article

Publication status: Published

Journal: Kidney International

Year: 2012

Volume: 82

Issue: 10

Pages: 1084-1092

Print publication date: 02/11/2012

Online publication date: 01/08/2012

ISSN (print): 0085-2538

ISSN (electronic): 1523-1755

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ki.2012.250

DOI: 10.1038/ki.2012.250

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