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

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. and Erger, F. and Skerka, C. and Wenzel, A. and Tschernoster, N. and Ehren, R. and Burgmaier, K. and Riehmer, V. and Licht, C. and Kirschfink, M. and Weber, L.T. and Altmueller, J. and 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
Page Range:197-206
Date:October 2020
Official Publication:https://doi.org/10.5414/CN110135
PubMed:View item in PubMed

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