Long-term data on two sisters with C3GN due to an identical, homozygous CFH mutation and autoantibodies

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Item Type:	Article
Title:	Long-term data on two sisters with C3GN due to an identical, homozygous CFH mutation and autoantibodies
Creators Name:	Hackl, A., Erger, F., Skerka, C., Wenzel, A., Tschernoster, N., Ehren, R., Burgmaier, K., Riehmer, V., Licht, C., Kirschfink, M., Weber, L.T., Altmueller, J., Zipfel, P.F. and Habbig, S.
Abstract:	C3 glomerulonephritis (C3GN) is a rare but severe form of kidney disease caused by fluid-phase dysregulation of the alternative complement pathway. Causative mutations in complement regulating genes as well as auto-immune forms of C3GN have been described. However, therapy and prognosis in individual patients remain a matter of debate and long-term data are scarce. This also applies for the management of transplant patients as disease recurrence post-transplant is frequent. Here, we depict the clinical courses of two sisters with the unique combination of an identical, homozygous mutation in the complement factor H (CFH) gene as well as autoantibodies with a clinical follow-up of more than 20 years. Interestingly, the sisters presented with discordant clinical courses of C3GN with normal kidney function in one (patient A) and end-stage kidney disease in the other sister (patient B). In patient B, eculizumab was administered immediately prior to and in the course after kidney transplantation, with the result of a stable graft function without any signs of disease recurrence. Comprehensive genetic work-up revealed no further disease-causing mutation in both sisters. Intriguingly, the auto-antibody profile substantially differed in both sisters: autoantibodies in patient A reduced the C3b deposition, while the antibodies identified in patient B increased complement activation and deposition of split products. This study underlines the concept of a personalized-medicine approach in complement-associated diseases after thorough evaluation of the individual risk profile in each patient.
Keywords:	Autoantibodies, Chronic Kidney Failure, Complement C3, Complement Factor H, Glomerulonephritis, Kidney, Mutation
Source:	Clinical Nephrology
ISSN:	0301-0430
Publisher:	Dustri
Volume:	94
Number:	4
Page Range:	197-206
Date:	October 2020
Official Publication:	https://doi.org/10.5414/CN110135
PubMed:	View item in PubMed

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