Abstract

BackgroundRheumatoid arthritis (RA) is an independent risk factor for cardiovascular diseases (CVD), driven by the underlying chronic systemic inflammation [1]. The imbalance of CD4+ T lymphocyte subsets, especially between T helper (Th) 17 cells and regulatory T (Treg) cells, can mediate autoimmune inflammatory process, promoting the overproduction of cytokines and abnormal antibodies [2,3]. However, the levels of peripheral Th17 and Treg cells in RA patients with CVD are still unknown.ObjectivesTo explore the expression of circulating Th17 and Treg cells in RA patients with CVD and analyze its clinical significance.MethodsA total of 192 patients with RA and 86 healthy controls (HCs) were enrolled from January 2019 to January 2021. The peripheral blood CD4+T lymphocyte subsets of all participants were assessed by flow cytometry. Patients were divided into RA-CVD group (n=72) and RA only group (n=120), and the clinical data were recorded. The statistical differences between two groups were analyzed by independent-samples t test, χ2 test or Mann-Whitney U test, and risk factors of CVD were analyzed using Logistic regression.Results① The median age and the percentage of male patients in the RA-CVD group were significantly higher than those in the RA only group. ② The absolute numbers of peripheral Treg cells in the patients with RA only and RA-CVD were all significantly lower than those in HCs [24.94(19.32, 34.12)cells/μl vs. 33.13(24.96, 45.83)cells/μl,Z=-4.135,P<0.01; 19.13(13.76, 27.34)cells/μl vs. 33.13(24.96, 45.83)cells/μl,Z=-5.354,P<0.01]. While the numbers of peripheral Th17 cells in two groups of patients were not significantly different with those in HCs. The ratios of Th17/Treg cells in two group patients were higher than those of HCs, but only the difference between RA-CVD patients and HCs were significant [0.40(0.23,0.63)vs. 0.18(0.13,0.29), Z=-4.696,P<0.01]. ③ Compared to the RA only patients, the absolute counts of Treg cells in RA-CVD patients were significantly lower [Z=-3.047,P<0.01], the numbers of Th17 cells were significantly higher [7.48(3.72, 13.63)cells/μl vs. 5.59(3.49,8.91)cells/μl,Z=-1.989,P<0.05], and the ratio of Th17/Treg cells was significantly higher [0.40(0.23,0.63)vs. 0.23(0.14,0.35),Z=-4.289,P<0.01]. ④ Logistic regression analysis showed that the level of circulating Treg cells (OR=0.936, 95%CI: 0.906-0.968) was a protective factor, while Th17 cells (OR=1.068, 95%CI: 1.020-1.119), elder age (OR=1.039, 95%CI: 1.004-1.076) and hypertension (OR=2.712, 95%CI: 1.254-5.865) were independent risk factors of RA patients complicated with CVD.ConclusionIt is suggested that the immune imbalance caused by the deficiency of Treg cells may be involved in the occurrence and development of RA complicated with CVD, and to restore Treg numbers and function may be a promising preventive strategies.

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