Background:Rheumatoid arthritis (RA) is a systemic autoimmune disease. It is characterized by highly disabling polyarthritis, but extra-articular features are also common and portend a poor prognosis. Compared with the general population, the incidence and mortality of cardiovascular disease in RA are significantly increased. Chronic autoimmune inflammation is the common pathogenesis of RA and coronary heart disease(CAD). We’ve proved that lymphocyte subsets imbalance and high cytokines expression play an important role in the occurrence and development of RA diseases. However, the level of lymphocyte subsets and cytokines of RA patients with CAD are rarely reported[1-2].Objectives:To explore the clinical characteristic of lymphocyte subsets and cytokines of RA patients with CAD,and make comparisons with simple RA patients and healthy controls.Methods:The study included 96 patients with a diagnosis of RA according to the 1987 revised criteria of the ACR, including 54 RA patients with CAD and 42 RA patients without CAD and other cardiovascular disease, 40 healthy controls are also concluded. The absolute numbers of lymphocyte subsets and T subsets in peripheral blood were measured by Flow Cytometer (FCM). Serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, INF-γ, and TNF-α were measured by flow microsphere capture chip technique (CBA) for 19 RA patients with CAD and 38 simple RA patients among 96 patients.We also collected relevant clinical information and made DAS28 score, and all patients are in the middle-high disease activity group (DAS28>3.2).Results:(1) There was no difference in DAS28 scores between the two groups(p=0.572). (2)Compared with RA patients without CAD, the absolute number of total T cell(P=0.035), total B cell (P=0.006), CD4+T cell(P=0.012), Th1 cell(P=0.037), Th17 cell(P=0.033) and CD4+CD25+FOXP3+ Treg(P=0.003) was lower than RA patients with CAD, the number of NK cell(P=0.685), CD8+T cell(P=0.322) and Th2 cell(P=0.770) had no obvious difference between them. (3)Compared with the healthy control, the absolute number of total T cell(P=0.014), total B cell (P=0.006), CD8+T cell(P=0.000) in RA with CAD was evidently lower, but there was no siginificant difference in absolute number of CD4+T cell(P=0.582), Th1 cell(P=0.052), Th2 cell(P=0.595), Th17 cell(P=0.148) and Treg(P=0.176) (Figure 1).(4) In RA patients with CAD,the level of cytokines IL-2(P=0.042), IL-4(P=0.043) and IL-17(P=0.012) was lower, while other cytokines had no difference (Table 1).Figure 1.The absolute number of lymphcytes of RA patients with CAD(n=54),RA patients without CAD (n=42) and healthy control (n=40). (*P<0.05,**P<0.01, ***P<0.001).Table 1.The expression level of cytokines of RA patients with CAD(n=19) and RA patients without CAD (n=38).Cytokines (pg/ml)RA and CAD group(A) (n = 19)RA group(B) (n = 38)PvalueA vs. BIL-25.50(1.96, 12.82)6.82(4.45, 14.44)0.042IL-44.93(1.67, 9.41)6.28(4.49, 11.88)0.043IL-623.69(10.93, 73.08)36.67(15.40, 72.50)0.636IL-107.76(4.54, 10.50)7.62(5.69, 19.91)0.223IL-1710.81(4.04, 20.25)20.68(13.88, 45.58)0.012IFN-γ6.10(3.27, 13.84)7.13(5.79, 15.83)0.115TNF-α10.49(2.50, 29.04)14.96(10.03, 30.39)0.097Conclusion:Our research shows that there is lymphocyte imbalance and immune disorder existing in RA patients with CAD. Both the number of lymphocyte subsets and cytokine levels decreased in these patients than pure RA patients. It suggests that this group may be in lower immune state, which providing guidance for further clinical treatment of RA patients with CAD.References:[1]Winchester R, Giles JT, Nativ S, et al. Association of Elevations of Specific T Cell and Monocyte Subpopulations in Rheumatoid Arthritis With Subclinical Coronary Artery Atherosclerosis. [J]. Arthritis Rheumatol, 2016,68(1): 92-102.[2]England BR, Thiele GM, Anderson DR, et al. Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications. [J]. BMJ, 2018 04 23;361.Disclosure of Interests:None declared
Background:The incidence of Ankylosing Spondylitis (AS) complicated with cardiovascular diseases (CVD) has increased in recent years [1]. However, identification of risk factors indicating the development of CAD in AS patients is lacking. Th17 cells are increasingly recognized to be important in atherogenesis [2]. However, the role of these cells in the pathogenesis of ankylosing spondylitis patients complicated with cardiovascular events remains elusive.Objectives:This study aimed to assess the level of circulating Th17 cells as well as other lymphocyte subsets such as Treg, Th, Ts, and NK cells in AS combined with CVD, and further to evaluate whether elevations in special PBMC subpopulations in AS patients indicate an increased risk of CVD.Methods:Samples were assessed from 141 AS patients hospitalized at the Second Hospital of Shanxi Medical University (60 AS patients combined with CVD and 81 AS patients without CVD) and 100 healthy controls. The absolute numbers of lymphocytes and CD4+ T cells in peripheral blood were determined using Flow Cytometer. The association between PBMC subpopulations and CVD development in AS patients were analyzed using multivariable logistic regression.Results:1. Compared with AS group, AS with CVD group exhibited significant increases in the number of Th17 cells (P=0.001) and Treg cells (P=0.046). The ratio of Th17/Treg was also increased (P=0.085).2. Analogous increases in the absolute number (P<0.001) and frequency (P<0.001) of Th1 cells, as well as the ratio of Th1/Th2 (P<0.001) and Th1/Treg (P=0.004) were also present in AS with CVD patients, compared to those without CVD.3. Compared to HCs, 141 AS patients showed significantly decreased Treg cells (P<0.012) and increased Th17/Treg (P=0.001).4. Logistic regression showed age (odds ratio: 1.09; 95% CI: 1.035-1.137), hypertension (odds ratio: 3.31; 95% CI: 1.152-9.528), diabetes (odds ratio: 8.03; 95% CI: 1.251-51.503), and elevated level of Th1 number (odds ratio: 1.01; 95% CI: 1.003-1.016) and DD (D-dimer) (odds ratio: 1.00; 95% CI: 1.000-1.002) were significantly correlated with the onset of CVD in AS patients.5. Smoke, increased Th17 level, and use of NSAIDS were also positively correlated with the onset of CVD although the P-values did not reach significant.Conclusion:Our data indicates aberrant expansion of Th17 cells in AS with CVD patients. Moreover, age, hypertension, diabetes, and increased level of Th1 in PBMC and DD are single independent risk factors for the presence of CVD in AS. The mechanisms of atherogenesis in AS may associate with the elevations in Th1 and Th17 cells. Imbalance of Th1/Th2 and Th17/Treg may be shared etiologic pathways of AS and CVD, providing attractive targets for the prevention and therapy of CVD development in AS patients.References:[1]Kim JH, Choi IA. Cardiovascular morbidity and mortality in patients with spondyloarthritis: A meta-analysis. Int J Rheum Dis (2020). doi: 10.1111/1756-185x.13970.[2]Saigusa R, Winkels H, Ley K. T cell subsets and functions in atherosclerosis. Nat Rev Cardiol. 2020 Jul;17(7):387-401. doi: 10.1038/s41569-020-0352-5.Figure 1.Compared with AS group, AS with CVD group exhibited significant increases in the number of Th17 cells (P=0.001) and Treg cells (P=0.046). The ratio of Th17/Treg was also increased (P=0.085). The absolute number (P<0.001) and frequency (P<0.001) of Th1 cells, as well as the ratio of Th1/Th2 (P<0.001) and Th1/Treg (P=0.004) were also present in AS with CVD patients.Disclosure of Interests:None declared.
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