The changes of intestinal flora and its relevance with memory Tfh and B cells in rheumatoid arthritis patients treated with csDMARDs and csDMARDs + bDMARDs

Abstract

Background

A growing body of experimental and clinical evidence has implicated gut microbiota in the onset and course of rheumatoid arthritis (RA). The imbalance of intestinal flora in RA patients may lead to abnormal expression of immune cells and related cytokines.

Purpose

Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and conventional synthetic disease-modifying antirheumatic drugs combined with biological disease-modifying antirheumatic drugs (csDMARDs + bDMARDs) are widely used to treat RA, but the characteristics of gut microbiota before and after treatment and their relationship with memory Tfh/B cells and cytokines remain unclear.

Methods

Stool samples were collected from 50 RA patients and 25 healthy controls (HCs) for 16SrRNA gene sequencing. We examined the proportion of lymphocyte subsets in healthy controls and RA patients. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of related cytokines in serum. The α and β diversity of intestinal flora, and the correlation between intestinal flora and clinical indicators, lymphocyte subsets, cytokines were analyzed.

Result

At the genus level, Ruminococcaceae_Ruminococcus was decreased in the csDMARDs and csDMARDs + bDMARDs treatment group, whereas Faecalibacterium was reduced in the csDMARDs treatment group, compared to untreated group. CD4⁺CD45RO⁺CCR7⁺CXCR5⁺central memory Tfh cells and CD4⁺CD45RO⁺CCR7^-CXCR5⁺effector memory Tfh cells were significantly lower in the csDMARDs + bDMARDs treatment group than in untreated group. CD19⁺CD27⁺IgD⁺pre-switched memory B cells were higher in the csDMARDs and csDMARDs + bDMARDs treatment groups, whereas CD19⁺CD27⁺IgD^-switched memory B cells were significantly lower than in untreated group. Ruminococcaceae_Ruminococcus was negatively correlated with CD19⁺CD27⁺IgD⁺ pre-switched memory B cells but positively correlated with CD4⁺CD45RO⁺CCR7^-CXCR5⁺effector memory Tfh and CD19⁺CD27⁺IgD^-switched memory B cells in patients with RA treated with DMARDs.

Conclusion

The gut microbiota, memory Tfh cells, memory B cells, and cytokines of patients with RA changed significantly under different treatment regimens and had certain correlations with the clinical indicators of RA.