黏膜相关恒定T细胞与2型糖尿病患者糖尿病肾脏病的相关性研究

Correlation between mucosal associated invariant T cells in peripheral blood and incidence of diabetic kidney disease in type 2 diabetes mellitus

目的探讨黏膜恒定相关T(MAIT)细胞与2型糖尿病(T2DM)患者糖尿病肾脏病(DKD)的相关性。方法为横断面研究。连续纳入2017年5—10月在浙江省人民医院门诊或病房就诊的初诊T2DM患者为研究对象。收集其尿白蛋白及尿肌酐并计算尿白蛋白/肌酐比值(UACR),检测其外周血总MAIT细胞比例、颗粒素酶B(Grmz-b)+MAIT细胞比例、活化指标CD69+MAIT细胞比例。根据研究对象是否合并DKD将其分为单纯T2DM组和DKD组,两组间比较采用两独立样本t检验或χ^(2)检验,采用Spearman相关性分析法分析外周血单个细胞中Grmz-b+MAIT细胞比例与UACR的相关性。结果共纳入129例未经治疗的初诊T2DM患者,其中单纯T2DM组70例,DKD组59例。两组间外周血总MAIT细胞占CD3^(+)T细胞比例差异有统计学意义(单纯T2DM组总MAIT细胞占CD3+细胞比例为3.27%±2.27%,DKD组为7.08%±5.05%,t=5.37,P<0.001)。DKD组CD69+MAIT细胞比例(21.64%±10.13%)高于单纯T2DM组(15.82%±6.64%)(t=2.47,P=0.014)。DKD组Grmz-b+MAIT细胞占总MAIT细胞比例(31.63%±10.00%)也高于单纯T2DM组(10.21%±6.63%)(t=14.04,P<0.001)。Spearman相关性分析结果显示,Grmz-b+MAIT细胞比例与UACR呈正相关(r=0.242,P=0.001)。结论MAIT细胞的活化比例增高与T2DM患者DKD的发生和发展密切相关。Grmz-b的高分泌可能与该病的发病有关。

Objective To clarify the relationship between mucosa-associated invariant T(MAIT)cells and the development of diabetic kidney disease(DKD)in type 2 diabetes mellitus(T2DM)patients.Methods This was a cross-sectional study.Consecutive patients aged 18-60 years with untreated T2DM who attended outpatients clinics or wards in People′s Hospital of Zhejiang Province were included as study subjects.Their urinary albumin and creatinine were collected and the urinary albumin-to-creatinine ratio(UACR)was calculated,and their peripheral blood total MAIT cell ratio,granzyme B(Grmz-b)+MAIT cell ratio,and activation index CD69+MAIT cell ratio were detected.Comparisons between the two groups were made using two independent samples t-test orχ^(2) test,and the correlation between the proportion of Grmz-b+MAIT cells in peripheral blood individual cells and UACR was analyzed using Spearman′s correlation analysis.Results A total of 129 untreated T2DM patients were included,including 70 patients with simple T2DM group and 59 patients with DKD(DKD group).There has significant difference in the total proportion of MAIT cells in peripheral blood between the DKD group and the T2DM group[(3.27%±2.27%)vs(7.08%±5.05%),t=5.37,P<0.001],and the proportions of CD69+MAIT cells[(21.64%±10.13%)vs(15.82%±6.64%),t=2.47,P=0.014]and Grmz-b+MAIT cells[(31.63%±10.00%)vs(10.21%±6.63%),t=14.04,P<0.001]were significantly higher in the DKD group than in the T2DM group.Correlation analysis found that the proportion of Grmz-b+MAIT cells was significantly positively correlated with the UACR(r=0.242,P=0.001).Conclusions The increased activation rate of mucosa-associated invariant T cells is closely related to the occurrence and development of DKD in patients with T2DM.The high secretion of Grmz-b may be related to its pathogenesis.