系统性红斑狼疮患者外周血CD4^＋CXCR5^＋滤泡辅助性T细胞样细胞的变化及糖皮质激素对其的影响

The abnormality and the effect of glucocorticoid treatment on CD4＋CXCR5＋ T cells in patients with systemic lupus erythematosus

目的研究系统性红斑狼疮（SLE）患者外周血CD4＋CXCR5＋T细胞占CD4＋T细胞百分率以及糖皮质激素对其的影响，探讨其在SLE发病机制中的作用。方法采用流式细胞术检测45例活动期、20例缓解期SLE患者及20名健康对照外周血中CD4＋CXCR5＋T细胞占CD4＋T细胞的百分率，比较其在各组中的差异及糖皮质激素治疗对其的影响，同时检测各组中CD19＋B细胞上CXCR5的表达。2组间比较用独立样本t检验，3组间比较采用多变量方差分析，与临床指标之间的相关性分析采用非参数的sDearman相关分析，治疗前后的差异用重复测量的方差分析。结果①SLE患者外周血CD4＋CXCR5＋T细胞占CD4＋T细胞的比例高于健康对照组[（16±7）％与（12±3）％，P〈0．01]，其中活动组[（18±7）％]高于健康对照组（P〈0．05），而缓解组[（11±4）％]和健康对照组之间差异无统计学意义（JD〉0．05）；狼疮肾炎组高于非狼疮肾炎组，但差异无统计学意义[（18±7）％与（14±7）％，P=0．05]。②CD4＋CXCR5＋T细胞百分率与SLE疾病活动指数（SLEDAI）、抗核抗体滴度和红细胞沉降率（ESR）呈正相关，与补体c3呈负相关（P均〈0．05），与C反应蛋白、病程、免疫球蛋白无相关性（P〉0．05）。抗双链DNA抗体升高组与正常组之间、抗Sm抗体、抗SSA／SSB抗体阴性组和阳性组之间差异无统计学意义（P均〉0．05）。③活动期SLE患者CD19＋B细胞卜CXCR5的表达比例低于健康对照组[（85±11）％与（94±3）％，P〈0．05]。④10例初发、未接受治疗的活动期患者在接受地塞米松（20mg／d）治疗后第1、3、7天外周血中CD4＋CXCR5＋T细胞百分率均低于治疗前（P均〈0．05）。治疗前后CD19＋CXCR5＋B细胞的百分率无变化（P均〉0．05）。结论外周血CD4＋CXCR5＋滤泡辅助性T细胞样细胞的异常可能参与SLE的发病。

Objective To investigate the frequencies of CD4＋CXCR5＋ T cells in the CD4＋ T cells of peripheral blood Of patients with systemic lupus erythematosus （SLE） and ＇the effect of glueocorticoid on it. Methods Frequencies of CD4＋CXCR5＋T cell were analyzed by flow cytometry in 45 active, 20 inactive SLE patients and 20 healthy controls. Differences between groups and the effect of glucocorticoid were analyzed. Meanwhile, the expression of CXCR5 on CD19＋ B cells was analyzed. Independent sample t test was used for statistical analysis between twogroups, ANOVA was applied for data analysis between 3 groups,, non- parameterical Spearman＇s analysis was used for correlation analysis and repeated measurement ANOVA were used to compare the parameters before and after treatment. Results The percentage of CD4＋CXCR5＋ in CD4＋ T cells was increased in patients with SLE compared with healthy controls E（ 16±7）% vs （12±3）%, P〈0.01 ]. It was increased in patients with active SLE E（18±7）%3 compared with healthy controls （P〈0.05） but there was no significant difference between inactive SLE [（ 11±4）% ] and healthy controls（P〉0.05）. The percentage in patients with LN was higher than that in patients without LN, but without significant difference [ （18±7）% vs （14±7）%, P=-0.05 ]. The percentage of CD4＋CXCR5＋T cells was positively correlated with SLEDAI,the titer of ANA and level of ESR but negatively correlated with the level of C3 （P〈0.05 for each）. No correlation was found between duration and the levels of CRP and immunoglobulin.. The percentage in patients with high anti-dsDNA group was also higher than that of the low group, but no differences were found between anti-Sin antibody positive and negative groups neither between anti-SSA/SSB antibody positive and negative groups（P〉 0.05 for each）.The expression level of CXCR5 on CD19＋B cells in active SLE patients was lower than that of healthy controls [ （85±11）% vs （94-±3）%, P〈0.051. The percentages of CD4＋CXCR5＋T cells in 10 untreated active SLE patients were decreased at day 1, day 3 and day 7 after being treated with dexamethasone （20mg/d） when compared with those before the treatment （P〈0.05 for each）, but the percentages of CD19＋ CXCR5＋B cells had no significant change （P〉0.05 for each）. Conclusion These results demonstrate that the abnormality of CD4＋CXCR5＋T cells may play an important role in the pathogenesis of SLE.