Details

Autor(en) / Beteiligte

• Hackl, Agnes
• Erger, Florian
• Skerka, Christine
• Wenzel, Andrea
• Tschernoster, Nikolai
• Ehren, Rasmus
• Burgmaier, Kathrin
• Riehmer, Vera
• Licht, Christoph
• Kirschfink, Michael
• Weber, Lutz T
• Altmueller, Janine
• Zipfel, Peter F
• Habbig, Sandra

Titel

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

Ist Teil von

• Clinical nephrology, 2020-10, Vol.94 (4), p.197-206

Ort / Verlag

Germany

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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.