POS0549 IMBALANCED Tfr/Tfh IN PERIPHERAL BLOOD OF NEW-ONSET RHEUMATOID ARTHRITIS

Background Rheumatoid arthritis (RA) is a kind of autoimmune disease characterized with chronic aggressive arthritis, presence of abnormal antibodies and persistent synovitis[1]. However, the pathogenesis of RA remained unclear by now. Several observations have showed that the breakdown of immune tolerance was involved in the development of RA. T follicular regulatory (Tfr) cells and T follicular helper (Tfh) cells, as a new subset of CD4+T cell, can exert an opposite effect in the regulation of humoral immunity[2]. Intensive researches have showed that the imbalance of Tfr/Tfh cell is related to the pathogenesis and development of autoimmune disease. There is still a lack of understanding of the relationship between Tfr/Tfh and RA, which needs further exploration. Objectives To detect the expression of Tfh and Tfr cells in thr peripheral blood of patients with new-onset RA and healthy controls, and to explore the role of Tfh and Tfr cells in the pathogenesis and development of RA. Methods We enrolled 26 patients with new-onset RA who hospitalized at the Second Hospital of Shanxi Medical University from the June 2021 to the November 2021. And 17 age and gender-matched healthy adults were anticipated as controls. The absolute number of Tfh and Tfr cells in peripheral blood was detected by flow cytometry. Disease activity indicators were collected including erythrocyte sedimentation rate (ESR, mm/h) and Disease Activity Score in 28 joints (DAS28). Then we compared the expression of Tfh and Tfr cells between the patients and healthy controls and conducted the correlation analysis with disease activity. Results There was significant decreased level of Tfr cells in the patients with new-onset RA compared with healthy controls (P<0.001) and a lower ratio of Tfr/Tfh in the patients (P<0.01). The reduced Tfr cells and Tfr/Tfh were significant negative correlation with the disease activity indicators including ESR and DAS28 (r=-0.305, P=0.033). There was no statistically significant in the absolute number of Tfh cells between patients and healthy controls, but the level of Tfh cell showed an increasing trend in new-onset RA. Conclusion The results we investigated here showed that new-onset RA exhibited an imbalance of Tfr/Tfh, specifically reduced Tfr cells, compared with healthy controls, which were negatively correlated with higher disease activity in RA. It was likely that the imbalance of Tfr/Tfh in peripheral blood played an important role in the development of RA, which may be a target to treat RA. Table 1. A summary of data of all enrolled patients with RA and healthy controls HC(n=17) New-onset RA(n=26) P value Age(years) 51.94±13.03 55.88±13.56 P=0.35 Sex(male/female) 4/13 7/19 P=0.81 ESR(mm/h) a - 54.85±32.71 - DAS28 a - 5.09±1.56 - Tfh cell count(cell/UL) b 43.156(23.277,106.638) 83.914(38.133,119.662) 0.214 Tfr cell count(cell/UL) b 1.422(0.882,1.893) 0.441(0.116,2.888) 0.025 * Tfr/Tfh b 0.030(0.014,0.049) 0.011(0.001,0.024) 0.001 ** a Results are expressed as the mean ± standard error. b Results are expressed as the median(Q1,Q3). Normally distributed continuous variables were analyzed by the independent-samples Student’s t-test. And nonparametric variables were analyzed by Mann–Whitney U test Figure 1. The differences of Tfr and Tfh cells in peripheral blood between the healthy controls and patients with RA. Tfr cells were higher in new-onset RA leading to an imbalance of Tfr/Tfh. Statistical analyses were performed by the Mann-Whitney U test. (*P<0.05, **P<0.01) Figure 2. The correlation of disease activity with the level of Tfr cells and Tfr/Tfh. Tfr cells and Tfr/Tfh were negative associated with ESR and DAS28. Statistical analyses were performed by the Spearman correlation analysis. References [1]Sparks, J.A. Rheumatoid Arthritis [J]. Ann Intern Med, 2019, 170(1).DOI: 10.7326/AITC201901010. [2]Deng, J., Y. Wei, V.R. Fonseca, L. Graca, and D. Yu. T follicular helper cells and T follicular regulatory cells in rheumatic diseases [J]. Nat Rev Rheumatol, 2019, 15(8): 475-490.DOI: 10.1038/s41584-019-0254-2. Disclosure of Interests None declared.