Frontiers in Immunology (Sep 2021)
FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy
- Nóra Garam,
- Marcell Cserhalmi,
- Zoltán Prohászka,
- Zoltán Prohászka,
- Ágnes Szilágyi,
- Nóra Veszeli,
- Nóra Veszeli,
- Edina Szabó,
- Barbara Uzonyi,
- Attila Iliás,
- 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,
- Johannes Hofer,
- 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,
- Marijan Saraga,
- Tomáš Seeman,
- Jakub Zieg,
- Eva Sládková,
- Natasa Stajic,
- Tamás Szabó,
- Andrei Capitanescu,
- Simona Stancu,
- Miroslav Tisljar,
- Kresimir Galesic,
- András Tislér,
- Inga Vainumäe,
- Martin Windpessl,
- Tomas Zaoral,
- Galia Zlatanova,
- Mihály Józsi,
- Mihály Józsi,
- Dorottya Csuka,
- Dorottya Csuka
Affiliations
- Nóra Garam
- Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary
- Marcell Cserhalmi
- MTA-ELTE Complement Research Group, Eötvös Loránd Research Network (ELKH), Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary
- Zoltán Prohászka
- Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary
- Zoltán Prohászka
- Research Group for Immunology and Haematology, Semmelweis University-Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, Hungary
- Ágnes Szilágyi
- Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary
- Nóra Veszeli
- Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary
- Nóra Veszeli
- Research Group for Immunology and Haematology, Semmelweis University-Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, Hungary
- Edina Szabó
- Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary
- Barbara Uzonyi
- Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary
- Attila Iliás
- Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary
- Christof Aigner
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Alice Schmidt
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Martina Gaggl
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Gere Sunder-Plassmann
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- Dóra Bajcsi
- 1st Department of Internal Medicine, University of Szeged, Szeged, Hungary
- Jürgen Brunner
- Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria
- Alexandra Dumfarth
- Department of Medicine III: Nephrology, Transplant Medicine and Rheumatology, Geriatric Department, Ordensklinikum Linz-Elisabethinen, Linz, Austria
- Daniel Cejka
- Department of Medicine III: Nephrology, Transplant Medicine and Rheumatology, Geriatric Department, Ordensklinikum Linz-Elisabethinen, Linz, Austria
- Stefan Flaschberger
- Hospital of Klagenfurt, Klagenfurt, Austria
- Hana Flögelova
- 0Division of Nephrology, Department of Pediatrics, Faculty of Medicine, Palacky University and Faculty Hospital in Olomouc, Olomouc, Czechia
- Ágnes Haris
- 1Department of Nephrology, Péterfy Hospital, Budapest, Hungary
- Ágnes Hartmann
- 2Department of Pediatrics, University of Pécs, Pécs, Hungary
- Andreas Heilos
- 3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, Austria
- Thomas Mueller
- 3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, Austria
- Krisztina Rusai
- 3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, Austria
- Klaus Arbeiter
- 3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, Austria
- Johannes Hofer
- Department of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria
- Johannes Hofer
- 4Institute of Neurology of Senses and Language, Hospital of St John of God, Linz, Austria
- Johannes Hofer
- 5Research Institute for Developmental Medicine, Johannes Kepler University Linz, Linz, Austria
- Dániel Jakab
- 6Department of Pediatrics, University of Szeged, Szeged, Hungary
- Mária Sinkó
- 6Department of Pediatrics, University of Szeged, Szeged, Hungary
- Erika Szigeti
- 6Department of Pediatrics, University of Szeged, Szeged, Hungary
- Csaba Bereczki
- 6Department of Pediatrics, University of Szeged, Szeged, Hungary
- Viktor Janko
- 7Medimpax, Bratislava, Slovakia
- Kata Kelen
- 81st Department of Pediatrics, Semmelweis University, Budapest, Hungary
- György S. Reusz
- 81st Department of Pediatrics, Semmelweis University, Budapest, Hungary
- Attila J. Szabó
- 81st Department of Pediatrics, Semmelweis University, Budapest, Hungary
- Nóra Klenk
- 9Fresenius Medical Care (FMC) Center of Dialysis, Miskolc, Hungary
- Krisztina Kóbor
- 9Fresenius Medical Care (FMC) Center of Dialysis, Miskolc, Hungary
- Nika Kojc
- 0Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Maarten Knechtelsdorfer
- 1Department of Nephrology, Wilhelminenspital, Vienna, Austria
- Mario Laganovic
- 2Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia
- Adrian Catalin Lungu
- 3Pediatric Nephrology Department, Fundeni Clinical Institute, Bucharest, Romania
- Anamarija Meglic
- 4Department of Pediatric Nephrology, Division of Pediatrics, University Medical Center Ljubljana, Ljubljana, Slovenia
- Rina Rus
- 4Department of Pediatric Nephrology, Division of Pediatrics, University Medical Center Ljubljana, Ljubljana, Slovenia
- Tanja Kersnik Levart
- 4Department of Pediatric Nephrology, Division of Pediatrics, University Medical Center Ljubljana, Ljubljana, Slovenia
- Ernesta Macioniene
- 5Nephrology Center, Santaros Klinikos, Medical Faculty, Vilnius University, Vilnius, Lithuania
- Marius Miglinas
- 5Nephrology Center, Santaros Klinikos, Medical Faculty, Vilnius University, Vilnius, Lithuania
- Anna Pawłowska
- 6Department of Nephrology, Hypertension and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
- Tomasz Stompór
- 6Department of Nephrology, Hypertension and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland
- Ludmila Podracka
- 7Department of Pediatrics, Comenius University, Bratislava, Slovakia
- Michael Rudnicki
- 8Department of Internal Medicine IV-Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
- Gert Mayer
- 8Department of Internal Medicine IV-Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
- Romana Rysava
- 9Nephrology Clinic, 1st Faculty of Medicine, Charles University, Prague, Czechia
- Jana Reiterova
- 9Nephrology Clinic, 1st Faculty of Medicine, Charles University, Prague, Czechia
- Marijan Saraga
- 0Department of Pediatrics, University Hospital Split, Split, Croatia
- Marijan Saraga
- 1School of Medicine, University of Split, Split, Croatia
- Tomáš Seeman
- 2Department of Pediatrics, 2nd Faculty of Medicine, Charles University Prague, University Hospital Motol, Pragu, Czechia
- Jakub Zieg
- 2Department of Pediatrics, 2nd Faculty of Medicine, Charles University Prague, University Hospital Motol, Pragu, Czechia
- Eva Sládková
- 3Department of Pediatrics, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czechia
- Natasa Stajic
- 4Institute of Mother and Childhealth Care of Serbia “Dr Vukan Čupić”, Belgrade, Serbia
- Tamás Szabó
- 5Department of Pediatrics, Faculty of Medicine, Debrecen University, Debrecen, Hungary
- Andrei Capitanescu
- 6Carol Davila Nephrology Hospital, Bucharest, Romania
- Simona Stancu
- 6Carol Davila Nephrology Hospital, Bucharest, Romania
- Miroslav Tisljar
- 7Department of Nephrology, University Hospital Dubrava Zagreb, Zagreb, Croatia
- Kresimir Galesic
- 7Department of Nephrology, University Hospital Dubrava Zagreb, Zagreb, Croatia
- András Tislér
- 8Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
- Inga Vainumäe
- 9Department of Pathology, Tartu University Hospital, Tartu, Estonia
- Martin Windpessl
- 0Internal Medicine IV, Section of Nephrology, Klinikum Wels-Grieskirchen, Wels, Austria
- Tomas Zaoral
- 1Department of Pediatrics, University Hospital and Faculty of Medicine, Ostrava, Czechia
- Galia Zlatanova
- 2University Children’s Hospital, Medical University, Sofia, Bulgaria
- Mihály Józsi
- MTA-ELTE Complement Research Group, Eötvös Loránd Research Network (ELKH), Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary
- Mihály Józsi
- Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary
- Dorottya Csuka
- Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary
- Dorottya Csuka
- Research Group for Immunology and Haematology, Semmelweis University-Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, Hungary
- DOI
- https://doi.org/10.3389/fimmu.2021.720183
- Journal volume & issue
-
Vol. 12
Abstract
BackgroundFactor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data.MethodsA total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR).ResultsEight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters.ConclusionsOur observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.
Keywords
- membranoproliferative glomerulonephritis
- immune complex-mediated glomerulonephritis
- C3 glomerulopathy
- dense deposit disease (DDD)
- C3 glomerulonephritis (C3GN)
