AUTHOR=Garam Nóra , Cserhalmi Marcell , Prohászka Zoltán , Szilágyi Ágnes , 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 Ágnes , Hartmann Ágnes , 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 , Macioniene 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 

TITLE=FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.720183

DOI=10.3389/fimmu.2021.720183

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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 <italic>CFHR5</italic> 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.</p></sec><sec><title>Methods</title><p>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 <italic>CFHR5</italic> gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR).</p></sec><sec><title>Results</title><p>Eight exonic <italic>CFHR5</italic> 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.</p></sec><sec><title>Conclusions</title><p>Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.</p></sec>