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; A´gnes Szilágyi; 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; A´gnes Haris; A´gnes 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 Mačionienė; Marius Miglinas; Anna Pawłowska; Tomasz Stompór; Ludmila Podracka; Michael Rudnicki; Gert Mayer; Romana Rysava; Jana Reiterova; 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; Dorottya Csuka

doi:10.3389/fimmu.2021.720183

Title	FHR-5 serum levels and CFHR5 genetic variations in patients with immune complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy /
Authors	Garam, Nóra ; Cserhalmi, Marcell ; Prohászka, Zoltán ; Szilágyi, A´gnes ; Veszeli, Nóra ; Szabó, Edina ; Uzonyi, Barbara ; Iliás, Attila ; Aigner, Christof ; Schmidt, Alice ; Gaggl, Martina ; Sunder-Plassmann, Gere ; Bajcsi, Dóra ; Brunner, Jürgen ; Dumfarth, Alexandra ; Cejka, Daniel ; Flaschberger, Stefan ; Flögelova, Hana ; Haris, A´gnes ; Hartmann, A´gnes ; 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 ; Mačionienė, Ernesta ; Miglinas, Marius ; Pawłowska, Anna ; Stompór, Tomasz ; Podracka, Ludmila ; Rudnicki, Michael ; Mayer, Gert ; Rysava, Romana ; Reiterova, Jana ; Saraga, Marijan ; Seeman, Tomáš ; Zieg, Jakub ; Sládková, Eva ; Stajic, Natasa ; Szabó, Tamás ; Capitanescu, Andrei ; Stancu, Simona ; Tisljar, Miroslav ; Galesic, Kresimir ; Tislér, András ; Vainumäe, Inga ; Windpessl, Martin ; Zaoral, Tomas ; Zlatanova, Galia ; Józsi, Mihály ; Csuka, Dorottya
DOI	10.3389/fimmu.2021.720183
Full Text
Is Part of	Frontiers in immunology.. Lausanne : Frontiers Media S.A.. 2021, vol. 12, art. no. 720183, p. [1-20].. eISSN 1664-3224
Keywords [eng]	C3 glomerulonephritis (C3GN) ; C3 glomerulopathy ; dense deposit disease (DDD) ; immune complex-mediated glomerulonephritis ; membranoproliferative glomerulonephritis
Abstract [eng]	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.
Published	Lausanne : Frontiers Media S.A
Type	Journal article
Language	English
Publication date	2021
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„FHR-5 serum levels and CFHR5 genetic variations in patients with immune complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy /“