SLE患者外周血CD^4＋CD28^-、CD4^＋CD28^＋T细胞PD-1的表达及临床意义

Clinical significance of abnormally expressed PD-1 on CD4^＋CD28^- and CD4^＋CD28^＋ T cells in peripheral blood of SLE patients

目的探讨PD-1在系统性红斑狼疮（SLE）患者外周血CD4＋CD28－、CD4＋CD28＋T细胞上的表达及临床意义。方法收集50例初发SLE患者和40例正常对照外周血标本，PBMC法分离单个核细胞后，应用流式细胞仪分别检测两组外周血中CD4＋CD28－、CD4＋CD28＋、CD4＋CD28＋/－PD-1＋T细胞的百分比水平，详细记录SLE患者的临床资料，根据SLE疾病活动指数（SLEDAI）评分将SLE分为稳定组（SLEDAI〈10）和活动组（SLEDAI≥10），根据有、无肾脏损害分为狼疮肾炎组和无狼疮肾炎组，然后比较SLE活动组、稳定组和健康对照组以及有、无狼疮肾炎组之间细胞表达的百分比，统计学分析其与该病相关实验室参数、临床参数及与疾病活动指标间的相关性。结果SLE患者活动组外周血中CD4＋CD28－、CD4＋CD28＋PD-1＋、CD4＋CD28－PD-1＋T细胞表达水平高于稳定组和正常对照组（P〈0.05），狼疮肾炎组表达水平明显高于无狼疮肾炎组（P〈0.01）；SLE患者中抗dsDNA抗体阳性、抗SmRNP抗体阳性、补体C3降低、血小板减少和淋巴细胞减少组外周血CD4＋CD28－T细胞的表达水平均高于对应阴性组；患者中抗dsDNA抗体阳性、抗SmRNP抗体阳性、补体C3降低、补体C4降低和淋巴细胞减少组外周血CD4＋CD28＋PD-1＋T细胞的表达水平均高于对应阴性组；患者中抗dsDNA抗体阳性、补体C3降低、淋巴细胞减少以及脱发组外周血CD4＋CD28－PD-1＋T细胞的表达水平均高于对应阴性组，且差异均具有统计学意义（P〈0.05）。结论SLE患者外周血中CD4＋CD28－T细胞以及CD4＋CD28＋PD-1＋、CD4＋CD28－PD-1＋T细胞上PD-1出现异常表达，并且与该病相关实验室参数及临床指标存在一定的相关性。

ObjectiveTo investigate the clinical significance of abnormally expressed PD-1 on CD4＋ CD28＋ /-T cells in peripheral blood of patients with systemic lupus erythematosus （SLE）.MethodsPeripheral blood samples were collected form 50 patients with primary SLE and 40 healthy subjects and used to isolated mononuclear cells. Expression of CD4＋ CD28-, CD4＋ CD28＋ , CD4＋ CD28＋ PD-1＋ and CD4＋ CD28-PD-1＋ T cells in peripheral blood samples of the two groups were detected by flow cytometry. Clinical data of SLE patients were collected. Based on SLE disease activity index （SLEDAI）, SLE patients were classified into two groups： stable group （SLEDAI〈10） and active group （SLEDAI≥10）. Based on the condition of renal damage, they were also divided into two groups： lupus nephritis group and non-lupus nephritis group. Differences in T cell expression were compared among these groups. Statistical analysis was performed to analyze the relationships of different T cell subsets with laboratory and clinical parameters relating to SLE and SLEDAI.ResultsThe percentages of peripheral CD4＋ CD28-, CD4＋ CD28＋ PD-1＋ and CD4＋ CD28-PD-1＋ T cells of active group were higher than those of stable and healthy control groups （P〈0.05）. Moreover, patients with lupus nephritis had higher percentages of these T cell subsets than those without （P〈0.01）. SLE patients who were positive for anti-dsDNA or anti-SmRNP antibody, or had decreased complement C3, thrombocytopenia or decreased lymphocytes had higher percentages peripheral CD4＋ CD28-T cells than those in the corresponding negative group. SLE patients who were positive for anti-dsDNA or anti-SmRNP antibody, or had decreased complement C3, complement C4 or lymphocytes showed enhanced expression of peripheral CD4＋ CD28＋ PD-1＋ T cells as compared with those in the corresponding negative group. SLE patients positive for anti-dsDNA antibody, or with decreased complement C3 or lymphocytes or suffering from alopecia had higher percentages of peripheral CD4＋ CD28-PD-1＋ T cell than those in the corresponding negative group. Differences between different groups were statistically significant （P〈0.05）.ConclusionAbnormal expression of CD4＋ CD28-T cells and PD-1 on CD4＋ CD28- and CD4＋ CD28＋ T cells in peripheral blood of patients with SLE has certain correlation with laboratory parameters and clinical indicators.