慢性肾病患者外周血T淋巴细胞及NK细胞中TIGIT的表达和意义

Expression and significance of TIGIT in peripheral blood T lymphocytes and NK cells of patients with chronic kidney disease

目的探讨慢性肾病(CKD)患者外周血T淋巴细胞及NK细胞中基于T淋巴细胞免疫球蛋白和免疫受体酪氨酸的抑制性结构域(TIGIT)的表达及意义。方法选取2020年9月至2021年12月在江西中医药大学附属医院肾病科治疗的97例CKD 2~4期患者作为CKD组,同期体检的23例健康志愿者作为健康对照(HC)组。采用流式细胞术检测CD4^(+)T淋巴细胞、CD8^(+)T淋巴细胞、自然杀伤(NK)细胞TIGIT的表达水平,比较CKD组与HC组及不同CKD分期患者各淋巴细胞亚群TIGIT的表达差异。分析TIGIT的表达水平与临床实验室指标的相关性。结果与HC组相比,CKD组CD4^(+)T淋巴细胞、CD8^(+)T淋巴细胞以及NK细胞TIGIT的表达水平均升高(P<0.05)。CKD组CD4^(+)T淋巴细胞、CD8^(+)T淋巴细胞以及NK细胞TIGIT的表达水平随CKD分期的增加而有升高趋势,CKD 4期患者CD4^(+)T淋巴细胞TIGIT的表达水平高于CKD 3期和2期患者,差异均有统计学意义(P<0.05),CKD 4期患者CD8^(+)T淋巴细胞和NK细胞TIGIT表达水平高于CKD 2期患者,差异有统计学意义(P<0.05)。Pearson相关性分析显示:CD4^(+)T淋巴细胞数和CD8^(+)T淋巴细胞数分别与CD4^(+)T淋巴细胞和CD8^(+)T淋巴细胞TIGIT的表达水平呈负相关(P<0.05);CD4^(+)T淋巴细胞、CD8^(+)T淋巴细胞和NK细胞TIGIT的表达水平与估算的肾小球滤过率(eGFR)均呈负相关(P<0.05),与肌酐、胱抑素C呈正相关(P<0.05);CD4^(+)T淋巴细胞、NK细胞TIGIT表达水平与尿素氮呈正相关(P<0.05)。结论CKD患者外周血CD4^(+)T淋巴细胞、CD8^(+)T淋巴细胞和NK细胞TIGIT表达异常,而且TIGIT的表达与CKD分期及免疫系统功能障碍有关。

Objective To investigate the expression and significance of T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)in peripheral blood T lymphocytes and natural killer(NK)cells in patients with chronic kidney disease(CKD).Methods A total of 97 patients with CKD stage 2—4 who were treated in the Department of Nephrology,Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from September 2020 to December 2021 were enrolled as the CKD group,and 23 healthy volunteers who underwent physical examination during the same period were enrolled as the healthy control(HC)group.The expression levels of TIGIT in CD4^(+)T lymphocytes,CD8^(+)T lymphocytes and natural killer(NK)cells were detected by flow cytometry.The differences in the expression of TIGIT in lymphocyte subsets between CKD group and HC group and different stages of CKD patients were compared.The correlation between TIGIT expression level and clinical laboratory indicators was analyzed.Results Compared with the HC group,the CKD group had significant increases in the expression of TIGIT in CD4^(+)T lymphocytes,CD8^(+)T lymphocytes and NK cells(P<0.05).The expression level of TIGIT in CD4^(+)T lymphocytes,CD8^(+)T lymphocytes and NK cells in CKD group increased with the increase of CKD stage.The expression level of TIGIT in CD4^(+)T lymphocytes in CKD stage 4 patients was higher than that in CKD stage 3 and CKD stage 2 patients,and the differences were statistically significant(P<0.05).The expression level of TIGIT in CD8^(+)T lymphocytes and NK cells in CKD stage 4 patients was higher than that in CKD stage 2 patients,and the difference was statistically significant(P<0.05).Pearson correlation analysis showed that the number of CD4^(+)T lymphocytes and CD8^(+)T lymphocytes were negatively correlated with the expression level of TIGIT in CD4^(+)T lymphocytes and CD8^(+)T lymphocytes,respectively(P<0.05).The expression levels of TIGIT in CD4^(+)T lymphocytes,CD8^(+)T lymphocytes and NK cells were negatively correlated with estimated glomerular filtration rate(eGFR,P<0.05),and positively correlated with creatinine and cystatin C(P<0.05).The expression levels of TIGIT in CD4^(+)T lymphocytes and NK cells were positively correlated with urea nitrogen(P<0.05).Conclusion The expression of TIGIT in CD4^(+)T lymphocytes,CD8^(+)T lymphocytes and NK cells in peripheral blood of patients with CKD is abnormal,and the expression of TIGIT is related to CKD stage and immune system dysfunction.