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

Paixao Cavalcante, Danielle, López-Trascasa, Margarita, Skattum, Lillemor, Giclas, Patricia C, Goodship, Timothy H, de Córdoba, Santiago Rodríguez, Truedsson, Lennart, Morgan, Bryan Paul ORCID: and Harris, Claire Louise 2012. Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation. Kidney International 82 (10) , pp. 1084-1092. 10.1038/ki.2012.250

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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.

Item Type: Article
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: alternative pathway, complement, convertase, nephritic factor
Publisher: NPG
ISSN: 0085-2538
Last Modified: 08 May 2023 18:32

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