Case Report: A Rare Truncating Variant of the CFHR5 Gene in IgA Nephropathy.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_AA15A6D9CD84
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Case Report: A Rare Truncating Variant of the CFHR5 Gene in IgA Nephropathy.
Journal
Frontiers in genetics
Author(s)
Guzzo G., Sadallah S., Fodstad H., Venetz J.P., Rotman S., Teta D., Gauthier T., Pantaleo G., Superti-Furga A., Pascual M.
ISSN
1664-8021 (Print)
ISSN-L
1664-8021
Publication state
Published
Issued date
2021
Peer-reviewed
Oui
Volume
12
Pages
529236
Language
english
Notes
Publication types: Case Reports
Publication Status: epublish
Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Despite appropriate therapy, 20-40% of affected-patients evolve toward end-stage kidney disease (ESKD). Mesangial IgA deposits are the hallmark of IgAN, and complement deposition (C3) seems to differentiate latent IgA mesangial deposits from active IgAN. Atypical hemolytic uremic syndrome (aHUS), another disease in which complement plays an important role, is caused by inherited or acquired deregulation of the alternative pathway (AP) of complement. A subgroup of IgAN shows thrombotic microangiopathy (TMA) lesions in kidney biopsies, the histological characteristic of aHUS. Genetic variants of complement Factor H (CFH), known to be present in aHUS, have been associated with rapidly progressive forms of IgAN and a clinical pattern of aHUS. Genome-wide association studies (GWAS) have confirmed that the 1q32 region, encoding for CFH and its related proteins, is an IgAN susceptibility locus. A 30 year-old man was admitted for seizures and malignant hypertension. The kidney biopsy showed IgAN associated with features of TMA. Despite five plasma exchanges, the patient remained dialysis-dependent, and ESKD was diagnosed. Functional and genetic complement analysis were performed. A monoallelic protein-truncating, likely loss-of-function variant was identified in the CFHR5 gene. Eculizumab is the treatment of aHUS. As it has been successfully used in a few cases of rapidly progressive IgAN, it was decided to administer eculizumab over a period of 12 months in addition to the usual immunosuppression for renal transplantation. After a follow-up of 3 years, there was no clinical disease recurrence. Systematic biologic and genetic screening of complement in individuals with IgAN might be useful to better delineate the role of the AP of complement in renal disease progression, and this may have therapeutic implications.
Keywords
IgA nephropathy, complement, CFHR5, CFH, eculizumab, atypical hemolytic uremic syndrome, thrombotic microangiopathy (TA-TMA)
Pubmed
Web of science
Open Access
Yes
Create date
25/06/2021 17:39
Last modification date
07/07/2021 5:35
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