TIGIT、PD-1、CXCR5 CD4 T细胞增加与类风湿关节炎的疾病活动相关。
Increased TIGITPD‑1CXCR5CD4T cells are associated with disease activity in rheumatoid arthritis.
作者信息
Luo Qing, Fu Peng, Guo Yongqin, Fu Biqi, Guo Yang, Huang Qingshui, Huang Zikun, Li Junming
机构信息
Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Nanchang Key Laboratory of Diagnosis of Infectious Diseases, Nanchang, Jiangxi 330006, P.R. China.
出版信息
Exp Ther Med. 2022 Aug 31;24(4):642. doi: 10.3892/etm.2022.11579. eCollection 2022 Oct.
It is well established that increased programmed cell death protein 1 (PD-1)C-X-C chemokine receptor type 5 (CXCR5) CD4T cells are found in patients with rheumatoid arthritis (RA). T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) is a co-inhibitory receptor that is expressed on T cells. However, the expression patterns and immunomodulatory roles of TIGIT on PD1CXCR5CD4T cells in RA are poorly understood. Patients with RA were recruited and their clinical characteristics were recorded. The expression level of TIGIT on PD-1CXCR5CD4T cells was examined using flow cytometry. Subsequently, the correlation between various parameters of TIGITPD-1CXCR5CD4T cells [percentage of the cells, mean fluorescence intensity (MFI) of PD-1 and TIGIT in the cells] in patients with RA and clinical data, including autoantibodies, inflammatory indicators and RA activity, were analyzed. In addition, the risk factors of RA were assessed using univariate and multivariate regression analyses. The percentages of TIGITCXCR5CD4T, PD-1CXCR5CD4T, TIGITPD-1CXCR5CD4T, TIGITPD-1CXCR5CD4T cells, the MFI of PD-1 in these cells and the MFI of TIGIT in TIGITPD-1CXCR5CD4T cells were revealed to be significantly increased in patients with RA compared with those in healthy individuals. The parameters of TIGITPD-1CXCR5CD4T cells (percentage and/or MFI of PD-1) in patients with RA were found to be associated with the levels of anti-cyclic citrullinated peptide antibodies, rheumatoid factor and inflammatory markers, such as lymphocyte count, lymphocyte percentage, neutrophil percentage, lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio, systemic immune inflammation index, derived neutrophil-to-lymphocyte ratio, erythrocyte sedimentation rate and C-reactive protein. In addition, the MFI of PD-1 in TIGITPD-1CXCR5CD4T cells was associated with a disease activity score of 28 and the patient visual analogue scale. Multivariate logistic regression analysis demonstrated that the percentage of TIGITPD-1CXCR5CD4T cells and the MFI of PD-1 in TIGITPD-1CXCR5CD4T cells were risk factors for RA. The present study suggests that the increase in TIGITPD-1CXCR5CD4T cells is associated with the production of autoantibodies and RA activity and may serve a role in RA pathogenesis.
众所周知，类风湿关节炎（RA）患者体内程序性细胞死亡蛋白1（PD - 1）⁺C - X - C趋化因子受体5（CXCR5）⁺CD4⁺T细胞增多。具有免疫球蛋白和ITIM结构域的T细胞免疫受体（TIGIT）是一种在T细胞上表达的共抑制受体。然而，人们对TIGIT在RA患者PD1⁺CXCR5⁺CD4⁺T细胞上的表达模式和免疫调节作用了解甚少。招募了RA患者并记录其临床特征。使用流式细胞术检测PD - 1⁺CXCR5⁺CD4⁺T细胞上TIGIT的表达水平。随后，分析了RA患者中TIGIT⁺PD - 1⁺CXCR5⁺CD4⁺T细胞的各种参数[细胞百分比、细胞内PD - 1和TIGIT的平均荧光强度（MFI）]与临床数据之间的相关性，临床数据包括自身抗体、炎症指标和RA活动度。此外，使用单因素和多因素回归分析评估RA的危险因素。结果显示，与健康个体相比，RA患者中TIGIT⁺CXCR5⁺CD4⁺T、PD - 1⁺CXCR5⁺CD4⁺T、TIGIT⁺PD - 1⁺CXCR5⁺CD4⁺T、TIGIT⁻PD - 1⁺CXCR5⁺CD4⁺T细胞的百分比、这些细胞中PD - 1的MFI以及TIGIT⁺PD - 1⁺CXCR5⁺CD4⁺T细胞中TIGIT 的MFI均显著增加。发现RA患者中TIGIT⁺PD - 1⁺CXCR5⁺CD4⁺T细胞的参数（PD - 1的百分比和/或MFI）与抗环瓜氨酸肽抗体、类风湿因子和炎症标志物水平相关，如淋巴细胞计数、淋巴细胞百分比、中性粒细胞百分比、淋巴细胞与单核细胞比值、中性粒细胞与淋巴细胞比值、全身免疫炎症指数、衍生中性粒细胞与淋巴细胞比值、红细胞沉降率和C反应蛋白。此外，TIGIT⁺PD - 1⁺CXCR5⁺CD4⁺T细胞中PD - 1的MFI与疾病活动度评分28和患者视觉模拟量表相关。多因素逻辑回归分析表明，TIGIT⁺PD - 1⁺CXCR5⁺CD4⁺T细胞百分比和TIGIT⁺PD - 1⁺CXCR5⁺CD4⁺T细胞中PD - 1的MFI是RA的危险因素。本研究表明，TIGIT⁺PD - 1⁺CXCR5⁺CD4⁺T细胞的增加与自身抗体产生和RA活动度相关，可能在RA发病机制中起作用。
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