2019•Orphanet Journal of Rare DiseasesOpen access
C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy
Nóra Garam, Zoltán Prohászka, Ágnes Szilágyi, Christof Aigner, Alice Schmidt, Martina Gaggl, Gere Sunder–Plassmann, Dóra Bajcsi, Jürgen Brunner, Alexandra Dumfarth, Daniel Cejka, Stefan Flaschberger, Hana Flögelová, Agnès Haris, Ágnes Hartmann, Andreas Heilos, Thomas Mueller, Krisztina Rusai, Klaus Arbeiter, Johannes Hofer, Dániel Jakab, Mária Sinkó, Erika Szigeti, Csaba Bereczki, Viktor Jankó, Kata Kelen, György Reusz, Attila Jozsef Szabo, Nóra Klenk, Krisztina Kóbor, Nika Kojc, Maarten Knechtelsdorfer, Mario Laganović, Adrian Catalin Lungu, Anamarija Meglič, Rina R. Rus, Tanja Kersnik-Levart, Ernesta Mačionienė, Marius Miglinas, Anna Pawłowska, Tomasz P. Stompór, Ľudmila Podracká, Michael Rudnicki, Gert J. Mayer, Romana Ryšavá, Jana Reiterová, Marijan Saraga, Tomáš Seeman, Jakub Zieg, Eva Sládková, Tamás Szabó, Andrei Căpitănescu, Simona Hildegard Stancu, Miroslav Tišljar, Kres̆imir Gales̃ić, András Tislér, Inga Vainumäe, Martin Windpessl, Tomáš Zaoral, Galia Zlatanova, Dorottya Csuka
Abstract
BACKGROUND: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. RESULTS: One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. CONCLUSIONS: In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10-15% of IC-MPGN/C3G patients.