FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy
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 dys...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.720183/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Nóra Garam |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T19:16:17Z |
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| id | doaj.art-0c908e2545e94fcd87521ab9c91fb160 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T19:16:17Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0c908e2545e94fcd87521ab9c91fb1602022-12-21T21:35:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.720183720183FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-GlomerulopathyNóra Garam0Marcell Cserhalmi1Zoltán Prohászka2Zoltán Prohászka3Ágnes Szilágyi4Nóra Veszeli5Nóra Veszeli6Edina Szabó7Barbara Uzonyi8Attila Iliás9Christof Aigner10Alice Schmidt11Martina Gaggl12Gere Sunder-Plassmann13Dóra Bajcsi14Jürgen Brunner15Alexandra Dumfarth16Daniel Cejka17Stefan Flaschberger18Hana Flögelova19Ágnes Haris20Ágnes Hartmann21Andreas Heilos22Thomas Mueller23Krisztina Rusai24Klaus Arbeiter25Johannes Hofer26Johannes Hofer27Johannes Hofer28Dániel Jakab29Mária Sinkó30Erika Szigeti31Csaba Bereczki32Viktor Janko33Kata Kelen34György S. Reusz35Attila J. Szabó36Nóra Klenk37Krisztina Kóbor38Nika Kojc39Maarten Knechtelsdorfer40Mario Laganovic41Adrian Catalin Lungu42Anamarija Meglic43Rina Rus44Tanja Kersnik Levart45Ernesta Macioniene46Marius Miglinas47Anna Pawłowska48Tomasz Stompór49Ludmila Podracka50Michael Rudnicki51Gert Mayer52Romana Rysava53Jana Reiterova54Marijan Saraga55Marijan Saraga56Tomáš Seeman57Jakub Zieg58Eva Sládková59Natasa Stajic60Tamás Szabó61Andrei Capitanescu62Simona Stancu63Miroslav Tisljar64Kresimir Galesic65András Tislér66Inga Vainumäe67Martin Windpessl68Tomas Zaoral69Galia Zlatanova70Mihály Józsi71Mihály Józsi72Dorottya Csuka73Dorottya Csuka74Department of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryMTA-ELTE Complement Research Group, Eötvös Loránd Research Network (ELKH), Department of Immunology, ELTE Eötvös Loránd University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryResearch Group for Immunology and Haematology, Semmelweis University-Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryResearch Group for Immunology and Haematology, Semmelweis University-Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Immunology, ELTE Eötvös Loránd University, Budapest, HungaryDepartment of Immunology, ELTE Eötvös Loránd University, Budapest, HungaryDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, AustriaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, AustriaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, AustriaDivision of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria1st Department of Internal Medicine, University of Szeged, Szeged, HungaryDepartment of Pediatrics, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Medicine III: Nephrology, Transplant Medicine and Rheumatology, Geriatric Department, Ordensklinikum Linz-Elisabethinen, Linz, AustriaDepartment of Medicine III: Nephrology, Transplant Medicine and Rheumatology, Geriatric Department, Ordensklinikum Linz-Elisabethinen, Linz, AustriaHospital of Klagenfurt, Klagenfurt, Austria0Division of Nephrology, Department of Pediatrics, Faculty of Medicine, Palacky University and Faculty Hospital in Olomouc, Olomouc, Czechia1Department of Nephrology, Péterfy Hospital, Budapest, Hungary2Department of Pediatrics, University of Pécs, Pécs, Hungary3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, Austria3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, Austria3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, Austria3Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, AustriaDepartment of Pediatrics, Medical University of Innsbruck, Innsbruck, Austria4Institute of Neurology of Senses and Language, Hospital of St John of God, Linz, Austria5Research Institute for Developmental Medicine, Johannes Kepler University Linz, Linz, Austria6Department of Pediatrics, University of Szeged, Szeged, Hungary6Department of Pediatrics, University of Szeged, Szeged, Hungary6Department of Pediatrics, University of Szeged, Szeged, Hungary6Department of Pediatrics, University of Szeged, Szeged, Hungary7Medimpax, Bratislava, Slovakia81st Department of Pediatrics, Semmelweis University, Budapest, Hungary81st Department of Pediatrics, Semmelweis University, Budapest, Hungary81st Department of Pediatrics, Semmelweis University, Budapest, Hungary9Fresenius Medical Care (FMC) Center of Dialysis, Miskolc, Hungary9Fresenius Medical Care (FMC) Center of Dialysis, Miskolc, Hungary0Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia1Department of Nephrology, Wilhelminenspital, Vienna, Austria2Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia3Pediatric Nephrology Department, Fundeni Clinical Institute, Bucharest, Romania4Department of Pediatric Nephrology, Division of Pediatrics, University Medical Center Ljubljana, Ljubljana, Slovenia4Department of Pediatric Nephrology, Division of Pediatrics, University Medical Center Ljubljana, Ljubljana, Slovenia4Department of Pediatric Nephrology, Division of Pediatrics, University Medical Center Ljubljana, Ljubljana, Slovenia5Nephrology Center, Santaros Klinikos, Medical Faculty, Vilnius University, Vilnius, Lithuania5Nephrology Center, Santaros Klinikos, Medical Faculty, Vilnius University, Vilnius, Lithuania6Department of Nephrology, Hypertension and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland6Department of Nephrology, Hypertension and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland7Department of Pediatrics, Comenius University, Bratislava, Slovakia8Department of Internal Medicine IV-Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria8Department of Internal Medicine IV-Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria9Nephrology Clinic, 1st Faculty of Medicine, Charles University, Prague, Czechia9Nephrology Clinic, 1st Faculty of Medicine, Charles University, Prague, Czechia0Department of Pediatrics, University Hospital Split, Split, Croatia1School of Medicine, University of Split, Split, Croatia2Department of Pediatrics, 2nd Faculty of Medicine, Charles University Prague, University Hospital Motol, Pragu, Czechia2Department of Pediatrics, 2nd Faculty of Medicine, Charles University Prague, University Hospital Motol, Pragu, Czechia3Department of Pediatrics, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czechia4Institute of Mother and Childhealth Care of Serbia “Dr Vukan Čupić”, Belgrade, Serbia5Department of Pediatrics, Faculty of Medicine, Debrecen University, Debrecen, Hungary6Carol Davila Nephrology Hospital, Bucharest, Romania6Carol Davila Nephrology Hospital, Bucharest, Romania7Department of Nephrology, University Hospital Dubrava Zagreb, Zagreb, Croatia7Department of Nephrology, University Hospital Dubrava Zagreb, Zagreb, Croatia8Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary9Department of Pathology, Tartu University Hospital, Tartu, Estonia0Internal Medicine IV, Section of Nephrology, Klinikum Wels-Grieskirchen, Wels, Austria1Department of Pediatrics, University Hospital and Faculty of Medicine, Ostrava, Czechia2University Children’s Hospital, Medical University, Sofia, BulgariaMTA-ELTE Complement Research Group, Eötvös Loránd Research Network (ELKH), Department of Immunology, ELTE Eötvös Loránd University, Budapest, HungaryDepartment of Immunology, ELTE Eötvös Loránd University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryResearch Group for Immunology and Haematology, Semmelweis University-Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, HungaryBackgroundFactor 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.720183/fullmembranoproliferative glomerulonephritisimmune complex-mediated glomerulonephritisC3 glomerulopathydense deposit disease (DDD)C3 glomerulonephritis (C3GN) |
| spellingShingle | 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 FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy Frontiers in Immunology membranoproliferative glomerulonephritis immune complex-mediated glomerulonephritis C3 glomerulopathy dense deposit disease (DDD) C3 glomerulonephritis (C3GN) |
| title | FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy |
| title_full | FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy |
| title_fullStr | FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy |
| title_full_unstemmed | FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy |
| title_short | FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy |
| title_sort | fhr 5 serum levels and cfhr5 genetic variations in patients with immune complex mediated membranoproliferative glomerulonephritis and c3 glomerulopathy |
| topic | membranoproliferative glomerulonephritis immune complex-mediated glomerulonephritis C3 glomerulopathy dense deposit disease (DDD) C3 glomerulonephritis (C3GN) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.720183/full |
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fhr5serumlevelsandcfhr5geneticvariationsinpatientswithimmunecomplexmediatedmembranoproliferativeglomerulonephritisandc3glomerulopathy AT dorottyacsuka fhr5serumlevelsandcfhr5geneticvariationsinpatientswithimmunecomplexmediatedmembranoproliferativeglomerulonephritisandc3glomerulopathy AT dorottyacsuka fhr5serumlevelsandcfhr5geneticvariationsinpatientswithimmunecomplexmediatedmembranoproliferativeglomerulonephritisandc3glomerulopathy |