Hu Fanlei, Li Xin, Liu Kai, Li Yanpeng, Xie Yang, Wei Chaonan, Liu Shuyan, Song Jing, Wang Ping, Shi Lianjie, Li Chun, Li Jing, Xu Liling, Xue Jimeng, Zheng Xi, Bai Mingxin, Fang Xiangyu, Jin Xu, Cao Lulu, Hao Pei, He Jing, Wang Jun, Zhang Chiyu, Li Zhanguo
Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Ann Rheum Dis. 2024 Nov 14;83(12):1677-1690. doi: 10.1136/ard-2024-225564.
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.
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.
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 phage and 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.
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.
病毒被认为是类风湿关节炎（RA）发病机制中的重要参与者。然而，肠道病毒组的特征及其在RA中的作用仍不清楚。本研究旨在探究病毒组图谱及其在RA发病机制中的作用。
收集30对尽量减少遗传干扰的RA患者及其健康同胞的粪便样本进行宏基因组测序。分析病毒组的α和β多样性以及病毒组与细菌组的相互作用。鉴定差异噬菌体，并分析它们与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探究这些差异噬菌体在RA发病机制中的潜在作用。系统研究CD4 T细胞和B细胞对源自差异噬菌体的模拟表位的反应。
RA患者肠道噬菌体组的组成发生了改变。差异呈现的噬菌体与RA的免疫学特征相关，包括抗环瓜氨酸肽自身抗体和HLA-DR共享表位。有趣的是，甘油脂和嘌呤代谢基因在RA患者的噬菌体中高度活跃。此外，富含RA的噬菌体的肽，特别是噬菌体和噬菌体，可通过模拟疾病相关自身抗原表位，尤其是Bip的表位，引发CD4 T细胞和浆细胞的自身免疫反应。
本研究为RA发病过程中的肠道噬菌体组提供了新的见解。特别是，异常噬菌体表现出引发自身免疫的潜力，这可能促进疾病的发生。
