Rare Variants in Complement Gene in C3 Glomerulopathy and Immunoglobulin-Mediated Membranoproliferative GN
Copyright © 2023 by the American Society of Nephrology..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
---|---|
Enthalten in: |
Clinical journal of the American Society of Nephrology : CJASN - 18(2023), 11 vom: 01. Nov., Seite 1435-1445 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Meuleman, Marie Sophie [VerfasserIn] |
---|
Links: |
---|
Themen: |
80295-65-4 |
---|
Anmerkungen: |
Date Completed 09.11.2023 Date Revised 13.11.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.2215/CJN.0000000000000252 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM361143354 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM361143354 | ||
003 | DE-627 | ||
005 | 20231226084522.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.2215/CJN.0000000000000252 |2 doi | |
028 | 5 | 2 | |a pubmed24n1203.xml |
035 | |a (DE-627)NLM361143354 | ||
035 | |a (NLM)37615951 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Meuleman, Marie Sophie |e verfasserin |4 aut | |
245 | 1 | 0 | |a Rare Variants in Complement Gene in C3 Glomerulopathy and Immunoglobulin-Mediated Membranoproliferative GN |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 09.11.2023 | ||
500 | |a Date Revised 13.11.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 by the American Society of Nephrology. | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Complement C3 |2 NLM | |
650 | 7 | |a Complement Factor H |2 NLM | |
650 | 7 | |a 80295-65-4 |2 NLM | |
650 | 7 | |a Immunoglobulins |2 NLM | |
650 | 7 | |a Fibrinogen |2 NLM | |
650 | 7 | |a 9001-32-5 |2 NLM | |
700 | 1 | |a Vieira-Martins, Paula |e verfasserin |4 aut | |
700 | 1 | |a El Sissy, Carine |e verfasserin |4 aut | |
700 | 1 | |a Audard, Vincent |e verfasserin |4 aut | |
700 | 1 | |a Baudouin, Véronique |e verfasserin |4 aut | |
700 | 1 | |a Bertrand, Dominique |e verfasserin |4 aut | |
700 | 1 | |a Bridoux, Frank |e verfasserin |4 aut | |
700 | 1 | |a Louillet, Férielle |e verfasserin |4 aut | |
700 | 1 | |a Dossier, Claire |e verfasserin |4 aut | |
700 | 1 | |a Esnault, Vincent |e verfasserin |4 aut | |
700 | 1 | |a Jourde-Chiche, Noémie |e verfasserin |4 aut | |
700 | 1 | |a Karras, Alexandre |e verfasserin |4 aut | |
700 | 1 | |a Morin, Marie-Pascale |e verfasserin |4 aut | |
700 | 1 | |a Provot, François |e verfasserin |4 aut | |
700 | 1 | |a Remy, Philippe |e verfasserin |4 aut | |
700 | 1 | |a Ribes, David |e verfasserin |4 aut | |
700 | 1 | |a Rousset-Rouviere, Caroline |e verfasserin |4 aut | |
700 | 1 | |a Servais, Aude |e verfasserin |4 aut | |
700 | 1 | |a Thervet, Eric |e verfasserin |4 aut | |
700 | 1 | |a Tricot, Leila |e verfasserin |4 aut | |
700 | 1 | |a Zaidan, Mohamad |e verfasserin |4 aut | |
700 | 1 | |a Wynckel, Alain |e verfasserin |4 aut | |
700 | 1 | |a Zuber, Julien |e verfasserin |4 aut | |
700 | 1 | |a Le Quintrec, Moglie |e verfasserin |4 aut | |
700 | 1 | |a Frémeaux-Bacchi, Véronique |e verfasserin |4 aut | |
700 | 1 | |a Chauvet, Sophie |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Clinical journal of the American Society of Nephrology : CJASN |d 2006 |g 18(2023), 11 vom: 01. Nov., Seite 1435-1445 |w (DE-627)NLM172123720 |x 1555-905X |7 nnns |
773 | 1 | 8 | |g volume:18 |g year:2023 |g number:11 |g day:01 |g month:11 |g pages:1435-1445 |
856 | 4 | 0 | |u http://dx.doi.org/10.2215/CJN.0000000000000252 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 18 |j 2023 |e 11 |b 01 |c 11 |h 1435-1445 |