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.
Keywords: C3 glomerulonephritis (C3GN); C3 glomerulopathy; dense deposit disease (DDD); immune complex-mediated glomerulonephritis; membranoproliferative glomerulonephritis.
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.