Rare Variants in Complement Gene in C3 Glomerulopathy and Immunoglobulin-Mediated Membranoproliferative GN Article Swipe
Marie-Sophie Meuleman
,
Paula Vieira-Martins
,
Carine El Sissy
,
Vincent Audard
,
Véronique Baudouin
,
Dominique Bertrand
,
Frank Bridoux
,
Férielle Louillet
,
Claire Dossier
,
Vincent Esnault
,
Noémie Jourde‐Chiche
,
Alexandre Karras
,
Marie-Pascale Morin
,
François Provôt
,
Philippe Rémy
,
David Ribes
,
Caroline Rousset‐Rouvière
,
Aude Servais
,
Éric Thervet
,
Leïla Tricot
,
Mohamad Zaidan
,
Alain Wynckel
,
Julien Zuber
,
Moglie Le Quintrec
,
Véronique Frémeaux‐Bacchi
,
Sophie Chauvet
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.2215/cjn.0000000000000252
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.2215/cjn.0000000000000252
Background C3 glomerulopathy and idiopathic immunoglobulin-mediated membranoproliferative GN (Ig-MPGN) are rare complement-mediated kidney diseases. Inherited forms of C3 glomerulopathy/Ig-MPGN are rarely described. Methods Three hundred ninety-eight patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102) from a national registry were screened for three complement genes: factor H ( CFH ), factor I ( CFI ), and C3 . Patients with rare variant (minor allele frequency <0.1%) were included. Epidemiologic, clinical, and immunologic data at diagnosis and kidney outcomes of patients were retrospectively collected. Results Fifty-three different rare variants, including 30 (57%), 13 (24%), and ten (19%) in CFH , CFI , and C3 variants, were identified in 66/398 (17%) patients. Thirty-eight (72%) variants were classified as pathogenic, including 20/30 (66%) and 11/13 (84%) variants in CFH and CFI , respectively, impairing synthesis of factor H or factor I regulators. Fifteen of 53 (27%) variants were of unknown significance. At diagnosis, 69% of patients were adult (median age of 31 years). With the exception of biologic stigma of thrombotic microangiopathy, which was more frequent in patients with CFI variants (5/14 [36%] versus 1/37 [3%] and 0% in the CFH group and C3 group, respectively, P < 0.001), the clinical and histologic features were similar among the three variants groups. The kidney outcome was poor regardless of the age at onset and treatment received. Sixty-five percent (43/66) of patients with rare variant reach kidney failure after a median delay of 41 (19–104) months, compared with 28% (55/195) after a median delay of 34 (12–143) months in the nonvariant group. Among 36 patients who received a kidney transplant, 2-year recurrence was frequent, occurring in 39% (12/31), without difference between variant groups, and led to graft failure in three cases. Conclusions In our cohort, 17% of C3 glomerulopathy/Ig-MPGN cases were associated with rare variants in the CFH , CFI , or C3 genes. In most cases, a quantitative deficiency in factor H or factor I was identified. The presence of a rare variant was associated with poor kidney survival. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_08_CJN0000000000000252.mp3
Related Topics
Concepts
Membranoproliferative glomerulonephritis
Medicine
Glomerulopathy
Complement (music)
Complement system
Antibody
Immunology
Gene
Immunoglobulin G
Genetics
Glomerulonephritis
Phenotype
Biology
Kidney
Internal medicine
Complementation
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.2215/cjn.0000000000000252
- OA Status
- green
- Cited By
- 18
- References
- 32
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386117068
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4386117068Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.2215/cjn.0000000000000252Digital Object Identifier
- Title
-
Rare Variants in Complement Gene in C3 Glomerulopathy and Immunoglobulin-Mediated Membranoproliferative GNWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-08-24Full publication date if available
- Authors
-
Marie-Sophie Meuleman, Paula Vieira-Martins, Carine El Sissy, Vincent Audard, Véronique Baudouin, Dominique Bertrand, Frank Bridoux, Férielle Louillet, Claire Dossier, Vincent Esnault, Noémie Jourde‐Chiche, Alexandre Karras, Marie-Pascale Morin, François Provôt, Philippe Rémy, David Ribes, Caroline Rousset‐Rouvière, Aude Servais, Éric Thervet, Leïla Tricot, Mohamad Zaidan, Alain Wynckel, Julien Zuber, Moglie Le Quintrec, Véronique Frémeaux‐Bacchi, Sophie ChauvetList of authors in order
- Landing page
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https://doi.org/10.2215/cjn.0000000000000252Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.ncbi.nlm.nih.gov/pmc/articles/10637453Direct OA link when available
- Concepts
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Membranoproliferative glomerulonephritis, Medicine, Glomerulopathy, Complement (music), Complement system, Antibody, Immunology, Gene, Immunoglobulin G, Genetics, Glomerulonephritis, Phenotype, Biology, Kidney, Internal medicine, ComplementationTop concepts (fields/topics) attached by OpenAlex
- Cited by
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18Total citation count in OpenAlex
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2025: 10, 2024: 8Per-year citation counts (last 5 years)
- References (count)
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32Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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