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, Ágnes Szilágyi, Nóra Veszeli, Edina K. Szabo, Barbara Uzonyi, Attila Iliás, Christof Aigner, Alice Schmidt, Martina Gaggl, Gere Sunder–Plassmann, Dóra Bajcsi, Jürgen Brunner, Alexandra Dumfarth, Daniel Cejka, Stefan Flaschberger, Hana Flögelová, Agnès Haris, Ágnes Hartmann, Andreas Heilos, Thomas Mueller, Krisztina Rusai, Klaus Arbeiter, Johannes Hofer, Dániel Jakab, Mária Sinkó, Erika Szigeti, Csaba Bereczki, Viktor Jankó, Kata Kelen, György Reusz, Attila J. Szabó, Nóra Klenk, Krisztina Kóbor, Nika Kojc, Maarten Knechtelsdorfer, Mario Laganović, Adrian Lungu, Anamarija Meglič, Rina Rus, Tanja Kersnik Levart, Ernesta Mačionienė, Marius Miglinas, Anna Pawłowska, Tomasz Stompór, Ľudmila Podracká, Michael Rudnicki, Gert Mayer, Romana Ryšavá, Jana Reiterová, Marijan Saraga, Tomáš Seeman, Jakub Zieg, Eva Sládková, Nataša Stajić, Tamás Szabó, Andrei Căpitănescu, Simona Stancu, Miroslav Tišljar, Kres̆imir Gales̃ić, András Tislér, Inga Vainumäe, Martin Windpessl, Tomáš Zaoral, Galia Zlatanova, Mihály Józsi, Dorottya Csuka
Abstract
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.