目的: 分析来自活动期和非活动期系统性红斑狼疮（systemic lupus erythematosus,SLE）患者以及正常对照组的CD4+CD28null T细胞、血小板结合补体裂解产物（platelet bound complement split product,PC4d）水平变化,并评估它们作为疾病活动和治疗效果判断的生物标志物的意义。方法: 这是一项在本院进行的单中心、观察性队列研究,研究时间为2021年1月—2022年6月,研究对象为15~70岁的90例SLE患者和22名健康对照。计算系统性红斑狼疮疾病活动指数（systemic lupus erythematosus disease activity index,SLEDAI）,以评估整体疾病活动;SLEDAI评分> 4分的患者视为活动期SLE,其余患者被归类为非活动期SLE。通过流式细胞术分析CD4+CD28null T细胞、PC4d水平。结果: 与健康对照组相比,活动性SLE组患者更年轻,CD4+CD28null T、PC4d水平更高。活动性SLE组和非活动性SLE组患者的WHO分级、SLEDAI、CD4+CD28null T细胞的差异有统计学意义。CD4+CD28null T、PC4d水平与SLEDAI呈显著正相关性（r=0.214, P<0.05; r=0.410, P<0.05）。不同WHO分级的CD4+CD28null T细胞百分比的差异有统计学意义,其中WHO 5级的CD4+CD28null T细胞百分比显著高于其他分级。与有治疗反应组相比,无治疗反应组的CD4+CD28null T、PC4d水平显著增加。ROC曲线显示CD4+CD28null T、PC4d预测活动期SLE治疗反应的AUC值分别为0.759（95%CI：0.604~0.914）、0.923（95%CI：0.832~1.000）。结论: CD4+CD28null T细胞群扩增和PC4d水平升高与SLE患者的疾病活动度密切相关,并且二者可作为预测活动性SLE患者治疗反应的潜在候选生物标志物。
Abstract
Objective To analyze the changes of CD4+CD28null T cells and platelet-bound complement cleavage products (PC4d) in patients with active and inactive systemic lupus erythematosus (SLE) and normal controls, and evaluate their significance as biomarkers for judging disease activity and therapeutic effect. Methods This was a single-center, observational cohort study in our hospital. The study time is from January 2021 to June 2022. The subjects were 90 SLE patients aged 15-70 and 22 healthy controls. Calculate systemic lupus erythematosus disease activity index (SLEDAI) to evaluate the overall disease activity; Patients with SLEDAI score>4 were regarded as active SLE, and the rest were classified as inactive SLE. The levels of CD4+CD28null T cells and PC4d were analyzed by flow cytometry. Results Compared with the healthy control group, the patients in active SLE group were younger, and the levels of CD4+CD28null T and PC4d were higher. The differences in WHO classification, SLEDAI, and CD4+CD28null T cells between patients with active SLE and those with inactive SLE were statistically significant. The levels of CD4+CD28null T and PC4d were positively correlated with SLEDAI (r=0.214, P<0.05; r=0.410, P<0.05). The difference in the percentage of CD4+CD28null T cells across different WHO classifications was statistically significant. and the percentage of CD4+CD28null T cells in WHO grade 5 was significantly higher than that in other grades. Compared with the group with treatment response, the levels of CD4+CD28null T and PC4d in the group without treatment response increased significantly. ROC curve showed that the AUC values of CD4+CD28null T and PC4d in predicting the treatment response of SLE in active stage were 0.759(95%CI: 0.604-0.914) and 0.923(95%CI: 0.832-1.000), respectively. Conclusion The expansion of CD4+CD28null T cell and the increase of PC4d level are closely related to the disease activity of SLE patients, and they can be used as potential candidate biomarkers to predict the treatment response of active SLE patients.
关键词
系统性红斑狼疮 /
活动期 /
CD4+CD28null T细胞 /
血小板结合补体裂解产物 /
治疗反应
Key words
systemic lupus erythematosus /
active phase /
CD4+CD28null T cells /
platelet-bound complement cleavage products /
treatment response
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基金
陕西省卫生健康委员会科研项目“人循环T免疫指数及血小板参数对系统性红斑狼疮治疗效果的预测价值”（2022E023）
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