C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

• Published in: Orphanet journal of rare diseases Vol. 14; no. 1; pp. 247 - 14
• Main Authors: Garam, Nóra, Prohászka, Zoltán, Szilágyi, Ágnes, Aigner, Christof, Schmidt, Alice, Gaggl, Martina, Sunder-Plassmann, Gere, Bajcsi, Dóra, Brunner, Jürgen, Dumfarth, Alexandra, Cejka, Daniel, Flaschberger, Stefan, Flögelova, Hana, Haris, Ágnes, Hartmann, Ágnes, Heilos, Andreas, Mueller, Thomas, Rusai, Krisztina, Arbeiter, Klaus, Hofer, Johannes, Jakab, Dániel, Sinkó, Mária, Szigeti, Erika, Bereczki, Csaba, Janko, Viktor, Kelen, Kata, Reusz, György S., Szabó, Attila J., Klenk, Nóra, Kóbor, Krisztina, Kojc, Nika, Knechtelsdorfer, Maarten, Laganovic, Mario, Lungu, Adrian Catalin, Meglic, Anamarija, Rus, Rina, Kersnik-Levart, Tanja, Macioniene, Ernesta, Miglinas, Marius, Pawłowska, Anna, Stompór, Tomasz, Podracka, Ludmila, Rudnicki, Michael, Mayer, Gert, Romana Rysava, Reiterova, Jana, Saraga, Marijan, Tomáš Seeman, Zieg, Jakub, Sládková, Eva, Szabó, Tamás, Capitanescu, Andrei, Stancu, Simona, Tisljar, Miroslav, Galesic, Kresimir, Tislér, András, Vainumäe, Inga, Windpessl, Martin, Zaoral, Tomas, Zlatanova, Galia, Csuka, Dorottya
• Format: Journal Article
• Language: English
• Published: London BioMed Central 08.11.2019; BioMed Central Ltd; BMC
• Subjects: Analysis; Antibodies; Autoantibodies; Autoimmunity; C3 glomerulonephritis; C3 glomerulopathy; C3 nephritic factor; C4 nephritic factor; Chronic kidney failure; Dense deposit disease; Development and progression; Glomerulonephritis; Human Genetics; Kidney diseases; Medical research; Medicine; Medicine & Public Health; Membranoproliferative glomerulonephritis; Pharmacology/Toxicology; Rare kidney diseases; C4 nephritic factor; C3 nephritic factor; Membranoproliferative glomerulonephritis; Dense deposit disease; C3 glomerulopathy; C3 glomerulonephritis
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-019-1237-8

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.