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
Abstract
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.
Funder
Magyar Tudományos Akadémia
Emberi Eroforrások Minisztériuma
Kidneeds
Subject
Immunology,Immunology and Allergy