The gut microbiota posttranslationally modifies IgA1 in autoimmune glomerulonephritis.

Autor:	Gleeson PJ; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France.; Department of Medicine, School of Microbiology, APC Microbiome Ireland, University College Cork, Cork T12 Y337 Ireland.; AP-HP, Nord/université de Paris, hôpital Bichat-Claude Bernard, Service de Néphrologie, Paris 75018, France., Benech N; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, Paris 75012, France.; Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris 75012, France.; Hospices Civils de Lyon, Claude Bernard Lyon 1 University, CRCL, 69003 Lyon, France., Chemouny J; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France.; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350 Jouy-en-Josas, France., Metallinou E; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France., Berthelot L; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France., da Silva J; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France., Bex-Coudrat J; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France., Boedec E; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France., Canesi F; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France., Bounaix C; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France., Morelle W; Université Lille, Centre National de la Recherche Française, UMR 8576-Unité de Glycobiologie Structurale et Fonctionnelle-Unité de Glycobiologie Structurale et Fonctionnelle, F-59000 Lille, France., Moya-Nilges M; Unité Technologie et Service Bioimagerie Ultrastructurale (UTechS UBI), Institut Pasteur, 28 Rue Du Docteur Roux, 75015 Paris, France., Kenny J; Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork P61 C996 Ireland.; APC Microbiome Ireland, University College Cork, College Road, Cork, T12 YT20 Ireland., O'Mahony L; Department of Medicine, School of Microbiology, APC Microbiome Ireland, University College Cork, Cork T12 Y337 Ireland., Saveanu L; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France., Arnulf B; AP-HP, Nord/université de Paris, hôpital Saint Louis, Service d'Immuno-Hématologie, Myosotis 4, 75010 Paris, France., Sannier A; AP-HP, Nord/université de Paris, hôpital Bichat-Claude Bernard, Service d'Anatomie-Pathologique, 75018 Paris, France., Daugas E; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France.; AP-HP, Nord/université de Paris, hôpital Bichat-Claude Bernard, Service de Néphrologie, Paris 75018, France., Vrtovsnik F; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France.; AP-HP, Nord/université de Paris, hôpital Bichat-Claude Bernard, Service de Néphrologie, Paris 75018, France., Lepage P; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350 Jouy-en-Josas, France., Sokol H; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Saint Antoine Hospital, Gastroenterology Department, Paris 75012, France.; Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris 75012, France.; Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350 Jouy-en-Josas, France., Monteiro RC; Université Paris Cité, INSERM UMR1149 and CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inflamex Laboratory of Excellence, Paris 75018, France.; AP-HP, Nord/université de Paris, hôpital Bichat-Claude Bernard, Service d'Immunologie, 75018 Paris, France.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2024 Mar 27; Vol. 16 (740), pp. eadl6149. Date of Electronic Publication: 2024 Mar 27.
DOI:	10.1126/scitranslmed.adl6149
Abstrakt:	Mechanisms underlying the disruption of self-tolerance in acquired autoimmunity remain unclear. Immunoglobulin A (IgA) nephropathy is an acquired autoimmune disease where deglycosylated IgA1 (IgA subclass 1) auto-antigens are recognized by IgG auto-antibodies, forming immune complexes that are deposited in the kidneys, leading to glomerulonephritis. In the intestinal microbiota of patients with IgA nephropathy, there was increased relative abundance of mucin-degrading bacteria, including Akkermansia muciniphila . IgA1 was deglycosylated by A. muciniphila both in vitro and in the intestinal lumen of mice. This generated neo-epitopes that were recognized by autoreactive IgG from the sera of patients with IgA nephropathy. Mice expressing human IgA1 and the human Fc α receptor I (α1 KI -CD89 tg ) that underwent intestinal colonization by A. muciniphila developed an aggravated IgA nephropathy phenotype. After deglycosylation of IgA1 by A. muciniphila in the mouse gut lumen, IgA1 crossed the intestinal epithelium into the circulation by retrotranscytosis and became deposited in the glomeruli of mouse kidneys. Human α-defensins-a risk locus for IgA nephropathy-inhibited growth of A. muciniphila in vitro. A negative correlation observed between stool concentration of α-defensin 6 and quantity of A. muciniphila in the guts of control participants was lost in patients with IgA nephropathy. This study demonstrates that gut microbiota dysbiosis contributes to generation of auto-antigens in patients with IgA nephropathy and in a mouse model of this disease.
Databáze:	MEDLINE
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