Naslov
FHR-5 serum levels and CFHR5 genetic variations in patients with immune complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

Autori
Garam, Nora ; Cserhalmi, Marcell ; Prohaszka, Zoltan ; Szilagyi, Agnes ; Veszeli, Nora ; Szabo, Edina ; Uzonyi, Barbara ; Ilias, Attila ; Aigner, Christof ; Schmidt, Alice ; Gaggl, Martina ; Sunder-Plassmann, Gere ; Bajcsi, Dora ; Brunner, Jurgen ; Dumfarth, Alexandra ; Cejka, Daniel ; Flaschberger, Stefan ; Floegelova, Hana ; Haris, Agnes ; Hartmann, Agnes ; Heilos, Andreas ; Mueller, Thomas ; Rusai, Krisztina ; Arbeiter, Klaus ; Hofer, Johannes ; Jakab, Daniel ; Sinko, Maria ; Szigeti, Erika Bereczki, Csaba ; Janko, Viktor ; Kelen, Kata ; Reusz, Gyoergy S. ; Szabo, Attila J. ; Klenk, Nora ; Kobor, Krisztina ; Kojc, Nika ; Knechtelsdorfer, Maarten ; Laganović, Mario ; Lungu, Adrian Catalin ; Meglić, Anamarija ; Rus, Rina ; Kersnik Levart, Tanja ; Macioniene, Ernesta ; Miglinas, Marius ; Pawlowska, Anna ; Stompor, Tomasz ; Podracka, Ludmila ; Rudnicki, Michael ; Mayer, Gert ; Rysava, Romana ; Reiterova, Jana ; Saraga, Marijan ; Seeman, Tomas ; Zieg, Jakub ; Sladkova, Eva ; Stajić, Nataša ; Szabo, Tamas ; Capitanescu, Andrei ; Stancu, Simona ; Tišljar, Miroslav ; Galešić, Krešimir ; Tisler, Andras ; Vainumae, Inga ; Windpessl, Martin ; Zaoral, Tomas ; Zlatanova, Galia ; Jozsi, Mihaly ; Csuka, Dorottya

Izvornik
Frontiers in Immunology (1664-3224) 12 (2021); 720183, 20

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
C3 glomerulonephritis (C3GN) ; C3 glomerulopathy ; dense deposit disease (DDD) ; immune complex-mediated glomerulonephritis ; membranoproliferative glomerulonephritis

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA