Objective:To investigate the expression and significance of programmed death receptor 1(PD-1) on T lymphocytes in patients with type 2 diabetic kidney disease(DKD).Methods: 80 healthy controls(NC group), 80 first diagnosis of type 2 diabetes mellitus patients(T2DM group), and 80 type 2 DKD patients(DKD group) were included in this study. According to urinary albumin creatinine ratio(UACR), the DKD group was divided into two subgroups, moderately elevated group(A2DKD group, UACR:30-300 mg·g-1) and severely elevated group(A3DKD group, UACR:>300 mg·g-1), with 40 cases in each subgroup. The expression rate of PD-1 on T lymphocytes subsets in peripheral blood were compared among the three groups. The correlation of estimated glomerular filtration rate(eGFR), serum creatinine(Scr) and UACR with expression rate of PD-1 on killer T lymphocytes was evaluated, and the expression rate of PD-1 on killer T lymphocytes of DKD patients before and after finerenone treatment were compared. Results: The expression rates of PD-1 in total T lymphocyte subset, helper T cell subset, killer T cell subset, and double negative T cell subset showed significant differences among the three groups(P<0.05). Further analysis of the expression rate of PD-1 in subgroups was found the expression rate of PD-1 in the killer T cell subset in the A3DKD group was significantly higher than that in the A2DKD group and T2DM group(all P<0.05). The expression rate of PD-1 in killer T cells was positively correlated with UACR(r=0.243, 95%CI:0.024-0.439) and Scr levels(r=0.507, 95%CI:0.323-0.654)(all P<0.05), but negatively correlated with eGFR level(r=-0.263, 95%CI:-0.456--0.046, P=0.02). After drug treatment, the expression rate of PD-1 in killer T cell subsets of DKD patients was significantly decreased(P<0.05). Conclusion: Increased expression of PD-1 in peripheral blood killer T cell subsets can lead to the progression of DKD, the rate of PD-1 expression in killer T cell subsets can be used as a biological indicator to evaluate the disease. |
[1] WANG Y,ZHAO H,WANG Q,et al.Chinese herbal medicine in ameliorating diabetic kidney disease via activating autophagy[J].J Diabetes Res,2019,2019:9030893.
[2] 王艳.T细胞在糖尿病肾病发展中作用的研究进展[J].现代医学,2022,50(11):1481-1485.
[3] 黄玲,田赛宁,杨梦婷,等.T细胞/PD-1/PD-L1通路在动脉粥样硬化免疫调控中的作用[J].医学综述,2022,28(12):2338-2344.
[4] 丁玥,陈金鹏,郑士亚.靶向PD-1/PD-L1相关免疫治疗在HER2阳性乳腺癌中应用的研究进展[J].东南大学学报(医学版),2024,43(3):473-478.
[5] ZHANG N,TAI J,QU Z,et al.Increased CD4+CXCR5+T follicular helper cells in diabetic nephropathy[J].Autoimmunity,2016,49(6):405-413.
[6] 中华医学会肾脏病学分会专家组.糖尿病肾脏疾病临床诊疗中国指南[J].中华肾脏病杂志,2021,37(3):255-304.
[7] LI H D,YOU Y K,SHAO B Y,et al.Roles and crosstalks of macrophages in diabetic nephropathy[J].Front Immunol,2022,13:1015142.
[8] 吴昊,顾敏娟,夏洪,等.2型糖尿病肾病患者外周血CD28/CTLA4共刺激分子的表达及及其意义[J].中国中西医结合肾病杂志,2020,21(2):120-122.
[9] GU Q W,SUN Q,WANG J,et al.Effects of glycemic variability on regulatory T cells in patients with type 2 diabetes and kidney disease[J].Diabetes Metab Syndr Obes,2023,16:2365-2375.
[10] 肖国辉,陈浪,李腾飞,等.PD-1单抗联合用药治疗肝细胞癌研究进展[J].医学研究杂志,2023,52(8):5-9.
[11] FARHOOD B,NAJAFI M,MORTEZAEE K.CD8+ cytotoxic T lymphocytes in cancer immunotherapy:a review[J].J Cell Physiol,2019,234(6):8509-8521.
[12] CHO H,KANG H,LEE H H,et al.Programmed cell death 1(PD-1) and cytotoxic T lymphocyte-associated antigen 4(CTLA-4) in viral hepatitis[J].Int J Mol Sci,2017,18(7):1517.
[13] BABAN B,LIU J Y,MOZAFFARI M S.Endoplasmic reticulum stress response and inflammatory cytokines in type 2 diabetic nephropathy:role of indoleamine 2,3-dioxygenase and programmed death-1[J].Exp Mol Pathol,2013,94(2):343-351.
[14] JIN J,WANG L,LIU Y,et al.Depiction of immune heterogeneity of peripheral blood from patients with type Ⅱ diabetic nephropathy based on mass cytometry[J].Front Endocrinol,2023,13:1018608.
[15] REYNOLDS J,SANDO G S,MARSH O B,et al.Stimulation of the PD-1/PDL-1 T-cell co-inhibitory pathway is effective in treatment of experimental autoimmune glomerulonephritis[J].Nephrol Dial Transplant,2012,27(4):1343-1350.
[16] WANG J,LIU H,YUE G,et al.Human placenta-derived mesenchymal stem cells ameliorate diabetic kidney disease by modulating the T helper 17 cell/regulatory T-cell balance through the programmed death 1 / programmed death-ligand 1 pathway[J].Diabetes Obes Metab,2024,26(1):32-45. |