Orphanet Journal of Rare Diseases (Nov 2019)
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 Flögelova,
- Ágnes Haris,
- Ágnes Hartmann,
- Andreas Heilos,
- Thomas Mueller,
- Krisztina Rusai,
- Klaus Arbeiter,
- Johannes Hofer,
- Dániel Jakab,
- Mária Sinkó,
- Erika Szigeti,
- Csaba Bereczki,
- Viktor Janko,
- Kata Kelen,
- György S. Reusz,
- Attila J. Szabó,
- Nóra Klenk,
- Krisztina Kóbor,
- Nika Kojc,
- Maarten Knechtelsdorfer,
- Mario Laganovic,
- Adrian Catalin Lungu,
- Anamarija Meglic,
- Rina Rus,
- Tanja Kersnik-Levart,
- Ernesta Macioniene,
- Marius Miglinas,
- Anna Pawłowska,
- Tomasz Stompór,
- Ludmila Podracka,
- Michael Rudnicki,
- Gert Mayer,
- Romana Rysava,
- Jana Reiterova,
- Marijan Saraga,
- Tomáš Seeman,
- Jakub Zieg,
- Eva Sládková,
- Tamás Szabó,
- Andrei Capitanescu,
- Simona Stancu,
- Miroslav Tisljar,
- Kresimir Galesic,
- András Tislér,
- Inga Vainumäe,
- Martin Windpessl,
- Tomas Zaoral,
- Galia Zlatanova,
- Dorottya Csuka
Affiliations
- Nóra Garam
- Research Laboratory, 3rd Department of Internal Medicine, and MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University
- Zoltán Prohászka
- Research Laboratory, 3rd Department of Internal Medicine, and MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University
- Ágnes Szilágyi
- Research Laboratory, 3rd Department of Internal Medicine, and MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University
- Christof Aigner
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
- Alice Schmidt
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
- Martina Gaggl
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
- Gere Sunder-Plassmann
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna
- Dóra Bajcsi
- 1st Department of Internal Medicine, University of Szeged
- Jürgen Brunner
- Department of Pediatrics, Medical University of Innsbruck
- Alexandra Dumfarth
- Department of Medicine III: Nephrology, Transplant Medicine and Rheumatology, Geriatric Department, Ordensklinikum Linz – Elisabethinen
- Daniel Cejka
- Department of Medicine III: Nephrology, Transplant Medicine and Rheumatology, Geriatric Department, Ordensklinikum Linz – Elisabethinen
- Stefan Flaschberger
- Hospital of Klagenfurt
- Hana Flögelova
- Division of Nephrology, Department of Pediatrics, Faculty of Medicine, Palacky University and Faculty Hospital in Olomouc
- Ágnes Haris
- Department of Nephrology, Szent Margit Hospital
- Ágnes Hartmann
- Department of Pediatrics, University of Pécs
- Andreas Heilos
- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna
- Thomas Mueller
- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna
- Krisztina Rusai
- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna
- Klaus Arbeiter
- Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna
- Johannes Hofer
- Department of Pediatrics, Medical University of Innsbruck
- Dániel Jakab
- Department of Pediatrics, University of Szeged
- Mária Sinkó
- Department of Pediatrics, University of Szeged
- Erika Szigeti
- Department of Pediatrics, University of Szeged
- Csaba Bereczki
- Department of Pediatrics, University of Szeged
- Viktor Janko
- Medimpax
- Kata Kelen
- 1st Department of Pediatrics, Semmelweis University
- György S. Reusz
- 1st Department of Pediatrics, Semmelweis University
- Attila J. Szabó
- 1st Department of Pediatrics, Semmelweis University
- Nóra Klenk
- FMC Center of Dialysis
- Krisztina Kóbor
- FMC Center of Dialysis
- Nika Kojc
- Institute of Pathology, Faculty of Medicine, University of Ljubljana
- Maarten Knechtelsdorfer
- 6th Department of Medicine, Nephrology and Dialysis, Wilhelminenspital
- Mario Laganovic
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hopital Center Zagreb, School of Medicine University of Zagreb
- Adrian Catalin Lungu
- Fundeni Clinical Institute
- Anamarija Meglic
- Department of Pediatric Nephrology, Division of Pediatrics, University Medical Centre Ljubljana
- Rina Rus
- Department of Pediatric Nephrology, Division of Pediatrics, University Medical Centre Ljubljana
- Tanja Kersnik-Levart
- Department of Pediatric Nephrology, Division of Pediatrics, University Medical Centre Ljubljana
- Ernesta Macioniene
- Nephrology Center, Santaros Klinikos, Medical Faculty, Vilnius University
- Marius Miglinas
- Nephrology Center, Santaros Klinikos, Medical Faculty, Vilnius University
- Anna Pawłowska
- Department of Nephrology, Hypertension and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury
- Tomasz Stompór
- Department of Nephrology, Hypertension and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury
- Ludmila Podracka
- Dept. of Pediatrics, Comenius University
- Michael Rudnicki
- Dept. of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck
- Gert Mayer
- Dept. of Internal Medicine IV - Nephrology and Hypertension, Medical University Innsbruck
- Romana Rysava
- Nephrology Clinic, 1st Faculty of Medicine, Charles University
- Jana Reiterova
- Nephrology Clinic, 1st Faculty of Medicine, Charles University
- Marijan Saraga
- Department of Pathology, University Hospital Split University of Split, School of Medicine
- Tomáš Seeman
- Department of Pediatrics, 2nd Faculty of Medicine, Charles University Prague, University Hospital Motol
- Jakub Zieg
- Department of Pediatrics, 2nd Faculty of Medicine, Charles University Prague, University Hospital Motol
- Eva Sládková
- Department of Pediatrics, Charles University in Prague, Faculty of Medicine in Pilsen
- Tamás Szabó
- Department of Pediatrics, University of Debrecen
- Andrei Capitanescu
- Carol Davila Nephrology Hospital
- Simona Stancu
- Carol Davila Nephrology Hospital
- Miroslav Tisljar
- Department of Nephrology, Dubrava University Hospital
- Kresimir Galesic
- Department of Nephrology, Dubrava University Hospital
- András Tislér
- 1st Department of Internal Medicine, Semmelweis University
- Inga Vainumäe
- Department of Pathology of Tartu University Hospital
- Martin Windpessl
- Internal Medicine IV, Section of Nephrology, Klinikum Wels-Grieskirchen
- Tomas Zaoral
- Department of Pediatrics, University Hospital and Faculty of Medicine Ostrava
- Galia Zlatanova
- University Children’s Hospital Medical University
- Dorottya Csuka
- Research Laboratory, 3rd Department of Internal Medicine, and MTA-SE Research Group of Immunology and Hematology, Hungarian Academy of Sciences and Semmelweis University
- DOI
- https://doi.org/10.1186/s13023-019-1237-8
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 14
Abstract
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.
Keywords
- C4 nephritic factor
- C3 glomerulopathy
- Membranoproliferative glomerulonephritis
- C3 nephritic factor
- Dense deposit disease
- C3 glomerulonephritis
