某种肠道细菌
肾病
免疫学
肠道菌群
免疫球蛋白A
肾小球肾炎
免疫系统
抗体
自身免疫性疾病
微生物学
生物
免疫球蛋白G
糖尿病
内分泌学
肾
作者
Patrick J. Gleeson,Nicolas Benech,Jonathan Chemouny,Eleftheria Theodora Metallinou,Laureline Berthelot,Jennifer Da Silva,Julie Bex-Coudrat,Erwan Boedec,Fanny Canesi,Carine Bounaix,Willy Morelle,Maryse Moya‐Nilges,John Kenny,Liam O’Mahony,Loredana Saveanu,Bertrand Arnulf,Aurélie Sannier,Éric Thervet,Jean-François Cordier,Patricia Lepage,Harry Sokol,Renato C. Monteiro
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2024-03-27
卷期号:16 (740)
被引量:5
标识
DOI:10.1126/scitranslmed.adl6149
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI