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1.	Paixao-Cavalcante, Danielle, et al. (author) Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation 2012 In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 82:10, s. 1084-1092 Journal article (peer-reviewed)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
2.	Paixao-Cavalcante, Danielle, et al. (author) Sensitive and specific assays for C3 nephritic factors permit dissection of mechanisms underlying complement dysregulation 2010 In: Molecular Immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 47:13, s. 96-96 Conference paper (peer-reviewed)

Paixao-Cavalcante, Danielle, et al. (author)
Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation
2012
In: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 82:10, s. 1084-1092
Journal article (peer-reviewed)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

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