重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对强直性脊柱炎患者外周血单个核细胞分泌功能的影响

目的探讨重组人Ⅱ型肿瘤坏死因子(TNF)受体-抗体融合蛋白(rhTNFR-Fc)治疗对强直性脊柱炎(AS)患者外周血单个核细胞分泌细胞因子功能的影响。方法于基线,第1、4次给药和停药(第8次给药)后20d收集rhTNFR-Fc开放性随机对照临床试验的10例AS患者(50mg,1次/周)和13名健康对照外周血,用酶联免疫斑点技术(ELISPOT)检测rhTNFR-Fc治疗前后AS患者及健康对照外周血分泌TNF-α、白细胞介素(IL)-2、IL-6和干扰素(IFN)-γ的T细胞数变化情况。并与AS活动指数(BASDAI)及其各子项目、AS功能指数(BASFI)、患者总体评价(PGA)、夜间痛、总体背痛、红细胞沉降率(ESR)、C反应蛋白(CRP)、血小板(PLT)等临床指标进行相关性分析。结果基线时分泌TNF-α、IL-2、IL-6和IFN-γ的T细胞数显著高于正常对照组(P值均<0.05),在给药后呈降低→升高→再降低的趋势,到停药后20d与基线时相比降低达到统计学意义。基线时分泌IL-6的细胞数与BASFI有显著的相关性;在给药第4次后,分泌TNF-α的细胞数与BASDAI-E有相关性,分泌IL-6的细胞数与BASDAI、夜间痛、总体背痛、BASDAI-E有显著相关性。结论 AS患者存在TNF-α、IL-6、IL-2、IFN-γ分泌功能的上调;rhTNFR-Fc治疗降低了AS患者T细胞分泌细胞因子的功能;分泌IL-6的细胞数与AS临床评价指标有一定相关性。

Experimental study of peripheral T cell cytokine secretion in ankylosing spondylitis after treatment with rhTNFR-Fc

Objective To study the effect of TNF-α antagonist （rhTNFR-Fc） treatment on the peripheral cy- tokine secretion in ankylosing spondylitis （AS）. Methods Peripheral blood mononuclear cells （PBMC） were collected from 10 patients with AS at baseline, after the first, fourth and eighth subcutaneous injections and 20 days after in- jection completion, and from 13 healthy controls. The number of T cells that secret TNF-α, IL-6, IFN-γ and IL-2 were detected by ELISPOT method. And their correlation with the clinical parameters including BASDAI, BASFI, PGA, night pain, ESR, CRP and PLT was analyzed. Rusults Compared to the healthy controls, the number of TNF-α, IL-6, IL-2, INF-γ producing cells was significant higher in AS patients （all P〈0.05） at baseline. A trend of de- crease-increase-decrease of TNF was observed after treatment. There was a significant decrease in the number of se- creting TNF-α, IL-6, IL-2, INF-γ cell 20 days after injection completion of rhTNFR-Fc treatment. At the baseline, the number of IL-6-secreting cells were correlated with BASFI. The number of IL-6-secreting cells after the fourth injection were correlated with BASDAI,night pain,global back pain,BASDAI-E. The number of TNF-α-secreting cells after the fourth injection were correlated with BASDAI-E. Conclusion AS patients had a up regulation of the ability of T cells to produce cytokine ; the treatment with rhTNFR-Fc in AS induced a down regulation of the ability of T cells to produce TNF-α, IL-6, IFN-γ and IL-2; the number of IL-6-secreting cells had significant correlation with clinical parameters.