Academic Journal
Association of Complement Genetics with Outcomes in IgA Nephropathy.
| Τίτλος: | Association of Complement Genetics with Outcomes in IgA Nephropathy. |
|---|---|
| Συγγραφείς: | Duval A; Inflammation, Complement and Cancer Team, Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université Paris Cité, Paris, France.; Department of Nephrology Dialysis and Transplantation, University Hospital of Strasbourg, Strasbourg, France.; Inserm UMR_1109, Molecular Immuno-Rheumatology, Centre de recherche en biomédecine, Université de Strasbourg, Strasbourg, France., Maillard N; Department of Nephrology Dialysis and Transplantation, University Hospital of Saint Etienne, Saint-Étienne, France.; Groupe sur l'immunité des muqueuses et agents pathogènes, Team 15, CIRI INSERM U1111/UMR5108., Morin M; INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Centrale Nantes, Nantes Université, Nantes, France., El Sissy C; Service d'immunologie biologique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France., Vieira-Martins P; Service d'immunologie biologique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France., Durand A; INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Centrale Nantes, Nantes Université, Nantes, France., Roquigny J; Inflammation, Complement and Cancer Team, Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université Paris Cité, Paris, France., Lecerf M; Inflammation, Complement and Cancer Team, Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université Paris Cité, Paris, France., Chauvet S; Inflammation, Complement and Cancer Team, Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université Paris Cité, Paris, France., Olagne J; Department of Nephrology Dialysis and Transplantation, University Hospital of Strasbourg, Strasbourg, France.; Department of Pathology, University Hospital of Strasbourg, Strasbourg, France., Moulin B; Department of Nephrology Dialysis and Transplantation, University Hospital of Strasbourg, Strasbourg, France., Roumenina L; Inflammation, Complement and Cancer Team, Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université Paris Cité, Paris, France., Limou S; INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Centrale Nantes, Nantes Université, Nantes, France., Mariat C; Department of Nephrology Dialysis and Transplantation, University Hospital of Saint Etienne, Saint-Étienne, France.; Groupe sur l'immunité des muqueuses et agents pathogènes, Team 15, CIRI INSERM U1111/UMR5108., Caillard S; Department of Nephrology Dialysis and Transplantation, University Hospital of Strasbourg, Strasbourg, France., Frémeaux-Bacchi V; INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Centrale Nantes, Nantes Université, Nantes, France. |
| Πηγή: | Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2026 Jul 01; Vol. 21 (7), pp. 1207-1221. Date of Electronic Publication: 2026 May 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wolters Kluwer Health Country of Publication: United States NLM ID: 101271570 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1555-905X (Electronic) Linking ISSN: 15559041 NLM ISO Abbreviation: Clin J Am Soc Nephrol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2023- : Hagerstown, MD : Wolters Kluwer Health Original Publication: Washington, D.C. : American Society of Nephrology, c2005- |
| Ιατρικοί όροι (MeSH): | Glomerulonephritis, IGA*/genetics , Glomerulonephritis, IGA*/immunology , Glomerulonephritis, IGA*/complications , Complement Factor H*/genetics , Complement System Proteins*/genetics, Membrane Cofactor Protein/genetics ; Complement Factor B/genetics ; Kidney Failure, Chronic/genetics ; Complement C3/genetics ; Complement Activation/genetics ; Humans ; Adult ; Female ; Male ; Haplotypes ; Middle Aged ; Genetic Predisposition to Disease ; Disease Progression ; Gene Frequency ; Homozygote ; Phenotype |
| Περίληψη: | Key Points: Activation of the alternative and lectin complement pathways contributes to disease severity and progression in IgA nephropathy. In this French cohort with severe IgA nephropathy, complement factor H CFH-H2 was underrepresented, and rare complement factor H missense variants were more frequent, affecting regulatory domains. Homozygosity for the membrane cofactor protein CD46 ggaac haplotype was associated with progression to ESKD, warranting confirmation in larger cohorts. Background: Complement activation plays a role in IgA nephropathy. Indeed, genome-wide association studies have identified a susceptibility locus for IgA nephropathy complement factor H ( CHF ) and its related proteins genes. However, the relationship between complement genetics and IgA nephropathy severity is not established. Methods: We sequenced 260 adults with a primary IgA nephropathy by next-generation sequencing of the CFH , complement factor I, complement factor B, membrane cofactor protein (encoded by CD46 ), C3 , and CFH related protein 5 genes. The frequencies of rare variants (minor allele frequency <0.1%) and CFH , membrane cofactor protein, and complement factor B haplotypes were compared with the European population from the 1000 Genomes Project. Functional in vitro studies were performed on recombinant full-length CFH variants. Results: Our genetic analysis revealed a higher prevalence of rare CFH nonsynonymous variants in patients with IgA nephropathy compared with controls (5% versus 2%, P = 0.03). In vitro studies showed impaired complement regulatory activity for five variants. The CFH-H2 haplotype was associated with lower IgA nephropathy susceptibility (odds ratio, 0.52 [0.34 to 0.79], P = 0.03, dominant model). Moreover, multivariable analysis revealed that the homozygous CD46 ggaaac haplotype was associated with ESKD 15 years after diagnosis (hazard ratio, 2.83; 95% confidence interval, 1.20 to 6.68; P = 0.02). Conclusions: Our study shed light on the dual role of complement genetics in IgA nephropathy. Our exploratory findings strengthen the evidence for a role of complement genetics in IgA nephropathy but will need confirmation in larger and independent studies. (Copyright © 2026 by the American Society of Nephrology.) |
| References: | Eur J Pediatr. 2011 Jan;170(1):107-10. (PMID: 20734203) J Am Soc Nephrol. 2026 Jun 01;37(6):1261-1272. (PMID: 41563799) Nat Genet. 2023 Jul;55(7):1091-1105. (PMID: 37337107) Front Immunol. 2021 Jan 14;11:602284. (PMID: 33519811) Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32. (PMID: 15870199) Clin J Am Soc Nephrol. 2013 Apr;8(4):554-62. (PMID: 23307876) Nephrol Dial Transplant. 2023 Jul 31;38(8):1789-1797. (PMID: 36307926) J Immunol. 2009 Jun 1;182(11):7009-18. (PMID: 19454698) Nat Genet. 2014 Nov;46(11):1187-96. (PMID: 25305756) Semin Immunol. 2019 Oct;45:101341. (PMID: 31757608) Nat Struct Mol Biol. 2011 Apr;18(4):463-70. (PMID: 21317894) Immunol Rev. 2023 Jan;313(1):25-45. (PMID: 36382387) Proc Natl Acad Sci U S A. 2021 Mar 30;118(13):. (PMID: 33753502) Cell. 2022 Sep 1;185(18):3426-3440.e19. (PMID: 36055201) Front Immunol. 2022 Mar 22;13:845953. (PMID: 35392081) Int Immunopharmacol. 2022 Nov;112:109234. (PMID: 36113314) Curr Opin Struct Biol. 2017 Jun;44:111-118. (PMID: 28189794) J Am Soc Nephrol. 2020 Dec;31(12):2949-2963. (PMID: 32912934) Front Immunol. 2021 Jun 10;12:638309. (PMID: 34177889) J Am Soc Nephrol. 2015 Jul;26(7):1503-12. (PMID: 25694468) Clin J Am Soc Nephrol. 2018 Sep 7;13(9):1330-1338. (PMID: 30042224) Nat Genet. 2016 Oct;48(10):1284-1287. (PMID: 27571263) Kidney Int. 2023 Aug;104(2):254-264. (PMID: 37263354) Nature. 2024 Jan;625(7993):92-100. (PMID: 38057664) Adv Chronic Kidney Dis. 2020 Mar;27(2):111-119. (PMID: 32553243) Am J Hematol. 2023 May;98 Suppl 4:S5-S19. (PMID: 36688486) Hum Genomics. 2021 Sep 25;15(1):60. (PMID: 34563268) Nephrol Dial Transplant. 2019 Apr 1;34(4):587-596. (PMID: 29635535) J Nephrol. 2022 May;35(4):1091-1100. (PMID: 34757577) Hum Mol Genet. 2009 Sep 15;18(18):3452-61. (PMID: 19549636) Kidney Int Rep. 2023 Jun 21;8(9):1730-1740. (PMID: 37705895) Nat Genet. 2011 Mar 13;43(4):321-7. (PMID: 21399633) Nat Rev Nephrol. 2013 Sep;9(9):523-8. (PMID: 23877587) Invest Ophthalmol Vis Sci. 2022 Nov 1;63(12):30. (PMID: 36445700) Nephrology (Carlton). 2019 Sep;24(9):885-895. (PMID: 30977248) J Am Soc Nephrol. 2016 Sep;27(9):2894-905. (PMID: 26825529) J Am Soc Nephrol. 2016 Oct;27(10):3187-3194. (PMID: 26940089) Front Immunol. 2015 Jun 02;6:262. (PMID: 26082779) Nephrol Ther. 2018 Apr;14 Suppl 1:S1-S8. (PMID: 29606255) J Am Soc Nephrol. 2015 May;26(5):1195-204. (PMID: 25205734) PLoS Genet. 2012;8(6):e1002765. (PMID: 22737082) J Am Soc Nephrol. 2018 Feb;29(2):661-669. (PMID: 29114042) Am J Kidney Dis. 2000 Aug;36(2):227-37. (PMID: 10922300) Curr Opin Immunol. 2021 Oct;72:126-134. (PMID: 34004375) Nephrol Dial Transplant. 2023 Sep 29;38(10):2340-2349. (PMID: 37156519) Kidney Int. 2022 Dec;102(6):1331-1344. (PMID: 36063874) Nephrol Dial Transplant. 2012 Apr;27(4):1479-85. (PMID: 21965586) Kidney Int Rep. 2022 Apr 04;7(6):1219-1228. (PMID: 35685318) Nat Rev Nephrol. 2021 Aug;17(8):543-553. (PMID: 33953366) Transfus Apher Sci. 2016 Apr;54(2):212-9. (PMID: 27177491) Clin Exp Immunol. 2008 Jan;151(1):1-13. (PMID: 18081690) Nephron. 2018;138(4):324-327. (PMID: 29241200) Am J Kidney Dis. 2026 Mar;87(3):412-421. (PMID: 41423086) Kidney Int. 2017 Oct;92(4):942-952. (PMID: 28673452) Kidney Int. 2016 Jan;89(1):167-75. (PMID: 26759049) Semin Immunopathol. 2021 Oct;43(5):707-715. (PMID: 34417628) Kidney Int. 2018 Feb;93(2):470-481. (PMID: 28941939) Kidney Int. 2017 Oct;92(4):953-963. (PMID: 28637589) PLoS Genet. 2012 Sep;8(9):e1002916. (PMID: 23028341) Nephrol Dial Transplant. 2003 Aug;18(8):1541-8. (PMID: 12897092) Kidney Int. 2017 May;91(5):1014-1021. (PMID: 28341274) Am J Hum Genet. 2002 Dec;71(6):1285-95. (PMID: 12424708) N Engl J Med. 2013 Jun 20;368(25):2402-14. (PMID: 23782179) Immunol Rev. 2023 Jan;313(1):71-90. (PMID: 36089777) BMC Nephrol. 2021 Jan 29;22(1):43. (PMID: 33514328) J Clin Med. 2021 Oct 14;10(20):. (PMID: 34682837) Clin J Am Soc Nephrol. 2023 Jun 1;18(6):727-738. (PMID: 37055195) Nephrol Dial Transplant. 2023 Nov 30;38(12):2685-2693. (PMID: 37385820) Nat Chem Biol. 2015 Jan;11(1):77-82. (PMID: 25402769) Mol Immunol. 2013 Dec 15;56(3):170-80. (PMID: 23830046) Pediatr Nephrol. 2019 Mar;34(3):533-537. (PMID: 30560448) Glomerular Dis. 2021 Oct 12;2(1):30-41. (PMID: 36751266) Nefrologia (Engl Ed). 2022 May-Jun;42(3):280-289. (PMID: 36154806) J Nephrol. 2023 Mar;36(2):495-505. (PMID: 35781866) Kidney Int Rep. 2025 Oct 08;11(1):207-218. (PMID: 41541767) PLoS Genet. 2017 Feb 10;13(2):e1006609. (PMID: 28187132) Front Immunol. 2023 Feb 09;14:1112257. (PMID: 36845135) J Am Soc Nephrol. 2019 Dec;30(12):2449-2463. (PMID: 31575699) Blood. 2021 Dec 2;138(22):2185-2201. (PMID: 34189567) Nephrol Dial Transplant. 2021 Jul 23;36(8):1389-1398. (PMID: 32582935) J Am Soc Nephrol. 2008 Mar;19(3):639-46. (PMID: 18235085) Am J Kidney Dis. 2013 Nov;62(5):883-90. (PMID: 23796906) Kidney Int. 2018 Jul;94(1):16-18. (PMID: 29933843) Blood. 2020 Sep 24;136(13):1558-1561. (PMID: 32488248) BJOG. 2023 Nov;130(12):1473-1482. (PMID: 37156755) Hum Mol Genet. 2005 Mar 1;14(5):703-12. (PMID: 15661753) |
| Grant Information: | FDM202006011155 FRM (fondation pour la recherche médicale); AO-AIRG-2016 AIRG |
| Contributed Indexing: | Keywords: GN; IgA nephropathy; complement; genetics and development; glomerular diseases; progression of kidney disease |
| Molecular Sequence: | ClinicalTrials.gov NCT05234463 |
| Substance Nomenclature: | 80295-65-4 (Complement Factor H) 0 (Membrane Cofactor Protein) 0 (CFH protein, human) 0 (CD46 protein, human) EC 3.4.21.47 (Complement Factor B) 0 (CFHR5 protein, human) 0 (Complement C3) 9007-36-7 (Complement System Proteins) |
| Entry Date(s): | Date Created: 20260515 Date Completed: 20260710 Latest Revision: 20260922 |
| Update Code: | 20260922 |
| PubMed Central ID: | PMC13379140 |
| DOI: | 10.2215/CJN.0000001062 |
| PMID: | 42138996 |
| Βάση Δεδομένων: | MEDLINE |
καταχωρήστε σχόλιο πρώτοι!