滤泡辅助性T细胞和相关分子在淋系恶性疾病中的变化及其意义  

The changes of follicular helper T ceils and their associated molecules in patients with malignant lymphoid diseases and their significances

作　　者：周东明[1] 徐燕霞[1] 袁育青[1] 陈萍[1] 孙谕[1] 傅晋翔[1] 

机构地区：[1]苏州大学附属第二医院血液科,215004

出　　处：《白血病．淋巴瘤》2016年第3期157-162,共6页Journal of Leukemia & Lymphoma

基　　金：国家自然科学基金（81272631）

摘　　要：目的动态分析淋系恶性疾病（MLD）患者外周血滤泡辅助性T细胞（Tfh细胞）变化，探讨其在预后判断中的作用。方法55例MLD患者纳入研究，其中急性淋巴细胞白血病（ALL）9例、非霍奇金淋巴瘤（NHL）30例、多发性骨髓瘤（MM）16例；以10名健康体检者为健康对照组。采用流式细胞术检测外周血CD4＋CXCR5＋细胞（Tfh细胞）占CD4＋细胞比例及诱导共刺激分子（ICOS）、程序性死亡蛋白1（PD-1）的表达；酶联免疫吸附法（ELISA）检测血浆白细胞介素21（IL-21）浓度。结果MLD患者治疗前Tfh细胞比例及ICOS、PD-1表达均高于健康对照组（均P〈0．01），MLD患者Tfh细胞比例及ICOS、PD-1表达水平由低至高依次为MM组、ALL组、NHL组。化疗第2、4、6个疗程末有效（完全缓解＋部分缓解）者Tth细胞比例及ICOS、PD-1表达水平总体呈下降趋势（P〈0．05），至第6个疗程末接近甚至低于健康对照组。第2个疗程末疾病进展患者Tfh细胞比例及ICOS、PD．1表达水平接近甚至高于治疗前水平。第6个疗程末获得完全缓解的ALL、NHL、MM患者Tih细胞比例及ICOS、PD-1表达水平更接近于健康对照组（P〉0．05），且低于部分缓解者（P〈0．05）。T细胞型ALL组和NHL组Tth细胞比例稍高于B细胞型，但差异无统计学意义（P〉0．05），且均高于健康对照组（P〈0．01）。ALL、NHL、MM患者血浆IL-21浓度[（474．55±33．41）Pg／ml、（498．64±68．11）Pg／ml、（445．08±36．14）Pg／m1]高于健康对照组[（326．56±32．44）Pg／ml，均P〈0．01]。Tfh细胞比例与骨髓中原始淋巴细胞＋幼稚淋巴细胞百分比、血清乳酸脱氢酶、国际预后指数、AnnArbor分期、ISS分期、8。微球蛋白呈正相关（r值分别为0．52、0．32、0．60、0．23、0．76、0．49，均P〈0．05）。结论ICOS、PD-1和IL-21表达异常所致外周血Tfh细胞过度活化可能参与了MLD的发病过程，Objective To investigate the changes of follicular helper T cells （Tfh cells） and Tfh cells associated molecules in the peripheral blood （PB） of patients with malignant lymphoid diseases （MLD） dynamically, and explore their roles on pathogenesis of the diseases. Methods Fifty-five patients with MLD were enrolled in this study,including 9 patients with acute lymphocyte leukemia （ALL）, 30 patients with non- Hodgkin lymophoma （NHL） and 16 patients with multiple myeloma （MM）, and 10 healthy controls （NC） of similar age were also enrolled. The percentage of CD4＋ CXCR5＋ cells （Tfh cells） and expression of ICOS＋, PD1＋ among the T cells were detected by flow cytometry （FCM）, while the levels of interleukin 21 （IL-21） in plasma were detected by ELISA tests. Results The percentage of Tfh cells and expression of ICOS and/or PD-1 in PB of all untreated patients were significantly higher than those of NC （all P 〈 0.01）, and MM group 〈 ALL group 〈NHL group. The levels of Tfh cells, ICOS and PD-1 in effective[complete remission （CR） ＋ partial remission （PR）] patients were presented a declining trend overall at the end of 2nd, 4th, 6th chemotherapy course （P 〈 0.05）. More so, the level might be close to even lower than the normal after the 6th course. The percentages of Tfh cells, ICOS and PD-1 in those patients who achieved disease progression （PD） at the end of 2nd course were close to even higher than before treatment. While at the end of 6th course the percentages who received CR were closer to those of NC （P 〉 0.05）, and apparently lower than those who achieved PR （P 〈 0.05）. The percentages of Tfh cells in patients with T-ALL and T-NHL were higher than those in patients with B-ALL and B-NHL （P 〉 0.05）, and much higher than NC （P 〈 0.01）. The concentration of IL-21 in patients were much higher than that in NC [（326.56±32.44） pg/ml] （P 〈 0.01）, and MM group〈ALL group〈NHL group [（445.08±36.14） pg/ml vs （

关 键 词：滤泡辅助性T细胞 CXCR5 诱导共刺激分子 程序性死亡蛋白1 白细胞介素21 

分 类 号：R733[医药卫生—肿瘤]