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Published on: January 29, 2014
C3 concentrations can be normal in patients with C3 glomerulopathy secondary to C3 nephritic factor
Hamish Anderson1, Mark Van Voorthuizen2, John O'Donnell2
1Immunology, Te Whatu Ora-Health New Zealand Canterbury Health Laboratories, Christchurch, New Zealand hamish.anderson@cdhb.health.nz.
Insights
C3 glomerulopathy (C3G) diagnosis can be challenging. Detecting C3 nephritic factors (C3Nef) is crucial, even with normal C3 levels, as low C3 is not always present.
Area of Science:
- Nephrology
- Immunology
- Complement System
Background:
- C3 glomerulopathy (C3G) involves glomerular C3 fragment deposition due to complement dysregulation.
- C3 nephritic factors (C3Nef) are a common acquired cause of C3G with prognostic implications.
Purpose of the Study:
- To investigate the relationship between C3 concentration and C3Nef detection in C3G patients.
- To highlight potential limitations in current C3 testing methods.
Main Methods:
- Retrospective analysis of positive C3Nef results since 2015.
- Review of biopsy-confirmed C3G cases with positive C3Nef.
Main Results:
- Two of four C3G patients with positive C3Nef had normal C3 concentrations.
- Commercial C3 testing may use antisera that detect both native C3 and breakdown products.
Conclusions:
- Normal C3 concentration should not prevent C3Nef testing in suspected C3G.
- Clinical context is vital for interpreting C3 levels and ordering C3Nef tests.
Abstract:
C3 glomerulopathy (C3G) is a rare kidney disease caused by the glomerular deposition of C3 fragments secondary to alternative pathway complement dysregulation. C3 nephritic factors (C3Nef) are the most common acquired cause, and their detection has treatment and prognostic implications. Although C3 concentration can be normal in the presence of C3Nef, many laboratories will only perform C3Nef testing when C3 is low. We performed a retrospective study of all positive C3Nef results from the authors' laboratory since 2015 and found that two of the four patients with positive C3Nef and biopsy-confirmed C3G had normal C3 concentrations. This may be in part due to limitations in commercial C3 testing methods which use anti-C3c antisera directed against both C3 breakdown products and native C3. A normal C3 concentration should not preclude C3Nef testing in the appropriate clinical context.
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