目的:探讨外周血CD4+CD25+CD127low调节性T细胞(regulatory T cells,Tregs)在多发性骨髓瘤(multiple myeloma,MM)治疗中的作用。方法:采用流式细胞术检测30例初治、27例完全缓解(CR)MM患者以及25例健康成年人外周血CD4+T细胞、Tregs数量,并检测Tregs表面功能分子CTLA-4及其凋亡相关蛋白CD95、bcl-2、Caspase3的表达,分析其与临床特点及疗效的关系。结果:初治组CD4+T细胞占外周血单个核细胞的比例低于对照组(P<0.05),Ⅲ期初治患者CD4+T细胞明显低于Ⅰ、Ⅱ期患者(P<0.05);初治MM组Tregs占CD4+T细胞比例显著高于CR组和正常对照组(P<0.05),初治Ⅲ期患者Tregs占CD4+T细胞比例明显高于初治Ⅰ、Ⅱ期患者(P<0.05)。初治组、CR组和正常对照组Tregs的表面CD95表达无统计学差异(P>0.05),初治组CTLA-4表达高于CR组(P<0.05)和对照组(P<0.01),CR患者CTLA-4高于对照组(P<0.05),初治组Tregs胞浆内bcl-2水平高于CR组(P<0.05)和对照组(P<0.01),CR组高于对照组(P<0.05),初治组和CR组Tregs胞内Caspase3的水平低于对照组(P<0.05)。初治组Tregs占CD4+比例与骨髓瘤数量呈正相关(P<0.05),且Tregs比例与治疗前后浆细胞下降值成反比(r=0.735,P<0.05)。结论:MM患者外周血Tregs水平升高,与瘤细胞负荷及疾病的分期呈正相关,与疗效呈负相关;Tregs水平增高与其抗凋亡能力增强有关。
OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.
