FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy
Copyright © 2021 Garam, Cserhalmi, Prohászka, Szilágyi, Veszeli, Szabó, Uzonyi, Iliás, Aigner, Schmidt, Gaggl, Sunder-Plassmann, Bajcsi, Brunner, Dumfarth, Cejka, Flaschberger, Flögelova, Haris, Hartmann, Heilos, Mueller, Rusai, Arbeiter, Hofer, Jakab, Sinkó, Szigeti, Bereczki, Janko, Kelen, Reusz, Szabó, Klenk, Kóbor, Kojc, Knechtelsdorfer, Laganovic, Lungu, Meglic, Rus, Kersnik Levart, Macioniene, Miglinas, Pawłowska, Stompór, Podracka, Rudnicki, Mayer, Rysava, Reiterova, Saraga, Seeman, Zieg, Sládková, Stajic, Szabó, Capitanescu, Stancu, Tisljar, Galesic, Tislér, Vainumäe, Windpessl, Zaoral, Zlatanova, Józsi and Csuka..
Background: Factor 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.
Methods: A 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).
Results: Eight 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.
Conclusions: Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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Enthalten in: |
Frontiers in immunology - 12(2021) vom: 28., Seite 720183 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Garam, Nóra [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 21.12.2021 Date Revised 21.12.2021 published: Electronic-eCollection Citation Status MEDLINE |
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doi: |
10.3389/fimmu.2021.720183 |
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funding: |
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PPN (Katalog-ID): |
NLM331086247 |
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245 | 1 | 0 | |a FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy |
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520 | |a Background: Factor 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 | ||
520 | |a Methods: A 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) | ||
520 | |a Results: Eight 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 | ||
520 | |a Conclusions: Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a C3 glomerulonephritis (C3GN) | |
650 | 4 | |a C3 glomerulopathy | |
650 | 4 | |a dense deposit disease (DDD) | |
650 | 4 | |a immune complex-mediated glomerulonephritis | |
650 | 4 | |a membranoproliferative glomerulonephritis | |
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700 | 1 | |a Sunder-Plassmann, Gere |e verfasserin |4 aut | |
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700 | 1 | |a Lungu, Adrian Catalin |e verfasserin |4 aut | |
700 | 1 | |a Meglic, Anamarija |e verfasserin |4 aut | |
700 | 1 | |a Rus, Rina |e verfasserin |4 aut | |
700 | 1 | |a Kersnik Levart, Tanja |e verfasserin |4 aut | |
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