Rheumatoid arthritis patients harbour aberrant enteric bacteriophages with autoimmunity-provoking potential: a paired sibling study.

IF 20.3 1区 医学 Q1 RHEUMATOLOGY
Fanlei Hu, Xin Li, Kai Liu, Yanpeng Li, Yang Xie, Chaonan Wei, Shuyan Liu, Jing Song, Ping Wang, Lianjie Shi, Chun Li, Jing Li, Liling Xu, Jimeng Xue, Xi Zheng, Mingxin Bai, Xiangyu Fang, Xu Jin, Lulu Cao, Pei Hao, Jing He, Jun Wang, Chiyu Zhang, Zhanguo Li
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Abstract

Objectives: Viruses have been considered as important participants in the development of rheumatoid arthritis (RA). However, the profile of enteric virome and its role in RA remains elusive. This study aimed to investigate the atlas and involvement of virome in RA pathogenesis.

Methods: Faecal samples from 30 pairs of RA and healthy siblings that minimise genetic interferences were collected for metagenomic sequencing. The α and β diversity of the virome and the virome-bacteriome interaction were analysed. The differential bacteriophages were identified, and their correlations with clinical and immunological features of RA were analysed. The potential involvement of these differential bacteriophages in RA pathogenesis was further investigated by auxiliary metabolic gene annotation and molecular mimicry study. The responses of CD4+ T cells and B cells to the mimotopes derived from the differential bacteriophages were systemically studied.

Results: The composition of the enteric bacteriophageome was distorted in RA. The differentially presented bacteriophages correlated with the immunological features of RA, including anti-CCP autoantibody and HLA-DR shared epitope. Intriguingly, the glycerolipid and purine metabolic genes were highly active in the bacteriophages from RA. Moreover, peptides of RA-enriched phages, in particular Prevotella phage and Oscillibacter phage could provoke the autoimmune responses in CD4+ T cells and plasma cells via molecular mimicry of the disease-associated autoantigen epitopes, especially those of Bip.

Conclusions: This study provides new insights into enteric bacteriophageome in RA development. In particular, the aberrant bacteriophages demonstrated autoimmunity-provoking potential that would promote the occurrence of the disease.

类风湿性关节炎患者体内存在具有自身免疫诱导潜能的异常肠道噬菌体:一项配对同胞研究。
目的:病毒一直被认为是类风湿性关节炎(RA)发病的重要参与者。然而,肠道病毒组的概况及其在 RA 中的作用仍然难以捉摸。本研究旨在调查类风湿关节炎发病机制中病毒组的图谱和参与情况:方法:收集 30 对 RA 和健康兄弟姐妹的粪便样本进行元基因组测序,以尽量减少遗传干扰。分析了病毒组的α和β多样性以及病毒组与细菌组之间的相互作用。鉴定了不同的噬菌体,并分析了它们与 RA 临床和免疫学特征的相关性。通过辅助代谢基因注释和分子模拟研究,进一步研究了这些差异噬菌体在RA发病机制中的潜在参与。系统研究了CD4+ T细胞和B细胞对来自差异噬菌体的模拟物的反应:结果:肠道噬菌体组的组成在RA中发生了扭曲。结果:RA患者肠道噬菌体组的组成发生了扭曲,不同的噬菌体与RA的免疫学特征相关,包括抗CCP自身抗体和HLA-DR共享表位。耐人寻味的是,RA噬菌体中的甘油脂和嘌呤代谢基因高度活跃。此外,富含RA的噬菌体,特别是普雷沃特氏菌噬菌体和奥希氏菌噬菌体的肽可通过分子模拟疾病相关的自身抗原表位,尤其是Bip的表位,激发CD4+ T细胞和浆细胞的自身免疫反应:这项研究为了解肠道噬菌体在 RA 发病过程中的作用提供了新的视角。结论:这项研究为了解肠道噬菌体组在 RA 发病过程中的作用提供了新的视角,尤其是噬菌体的异常表现出了诱发自身免疫的潜力,这将促进疾病的发生。
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来源期刊
Annals of the Rheumatic Diseases
Annals of the Rheumatic Diseases 医学-风湿病学
CiteScore
35.00
自引率
9.90%
发文量
3728
审稿时长
1.4 months
期刊介绍: Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
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