POS0396 THE LEVEL OF PERIPHERAL REGULATORY T CELLS IS ASSOCIATED WITH THE CHANGES OF INTESTINAL MICROBIOTA IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: R. Wu, J. An, T. Ding, H. Xue, X. F. Li, C. Wang
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is a systemic autoimmunity inflammation disease characterized with chronic aggressive arthritis and the presence of abnormal antibodies. Several observations showed that the breakdown of immune tolerance caused by many complex interactions was involved in the development of RA [1] . However, the pathogenesis of RA remained unclear. It has been confirmed that the imbalance of Th17 and Treg cells play a crucial role in destroying immune tolerance [2] . Besides, researches showed that intestinal microbiota can influence host immunity by acting on the immune cells to play pro-inflammatory or anti-inflammatory effect, and in turn immune system can also regulate the microbiota [3, 4] . Thus, a frontier point of view in the field of rheumatism, immune microecology, was proposed, which is a novel concept for the breakdown of immune tolerance. Studies have confirmed that there was an imbalance of intestinal microbiota in patients with RA [4] . But the relationship between the CD4+T subsets cells and intestinal microbiota in RA is unknown. Objectives: We detected and compared the absolute number of CD4+T cells subsets in the peripheral blood and the proportion or abundance of intestinal microbiota in patients with RA and healthy adults, and then analyzed the relationship between them to explore the role of CD4+T cells subsets and intestinal microbiota in the pathogenesis of RA. Methods: We collected the sample of stool and blood from 15 patients with RA hospitalized at the Second Hospital of Shanxi Medical University and 8 age and gender-matched healthy controls(HC). The absolute number of CD4+T cells subsets including Th1, Th2, Th17 and Treg cells were detected by flow cytometry. The 16S rRNA in the stool specimens were sequenced by the Roche/45 high-throughput sequencing platform. We analyzed whether there was correlarion between CD4+T subsets cells and intestinal microbiota. Results: Patients with RA had a higher level of Christensenellaceae and a lower level of Pseudomonadaceae as compared with those of HCs at the family level (p&lt;0.05). And at the genus level, the patients with RA had higher levels of Ruminococcus torques , Christensenellaceae R-7 , Ruminiclostridium 9 and Ruminococcus 1 compared with those of HCs (p&lt;0.05) (Figure 1).And the Ruminococcus torques at the genus level was negative correlated with the absolute number of Treg cells (p&lt;0.001) (Figure 2). Conclusion: The results here suggested that there were different proportion or abundance of intestinal microbiota between the patients with RA andHCs. And the changes of intestinal microbiota such as Ruminococcus torques were associated with Treg cells, further indicating that the imbalance of intestinal microbiota in RA can destory the immune tolerance. The above results uncovered that the intestinal microbiota had immunomodulatory function, which may be the upstream mechanism participated in the pathogenesis of RA. References: [1]Weyand CM, Goronzy JJ. The immunology of rheumatoid arthritis. Nat Immunol 2021, 22 (1): 10-18. [2]Weyand CM, Goronzy JJ. Immunometabolism in the development of rheumatoid arthritis. Immunol Rev 2020, 294 (1): 177-187. [3]Brown EM, Kenny DJ, Xavier RJ. Gut Microbiota Regulation of T Cells During Inflammation and Autoimmunity. Annu Rev Immunol 2019, 37: 599-624. [4]du Teil Espina M, Gabarrini G, Harmsen HJM, Westra J, van Winkelhoff AJ, van Dijl JM. Talk to your gut: the oral-gut microbiome axis and its immunomodulatory role in the etiology of rheumatoid arthritis. FEMS Microbiol Rev 2019, 43 (1). Figure 1. At the family level (a-b) and the genus level(c-f), the relative abundance of intestinal microbiota in patients with RA and HCs were different. Data were expressed as median (Q1, Q3) and analyzed by Wilcoxon test. (*** P &lt; 0.001, **P &lt; 0.01 and *P &lt; 0.05). Figure 2. A heatmap shows the correlation between the intestinal microbiota and CD4+T cells in patients with RA, and Ruminococcus torques at the genus level was negative related with Treg cells. (Colors indicate the Spearman rank correlation, *** P &lt; 0.001). Disclosure of Interests: None declared