UC-MSC联合利妥昔单抗及甲强龙对系统性红斑狼疮免疫炎性易栓状态的影响作用

目的初步探讨脐带间充质干细胞（umbilical cord mesenchymal stem cells,UC-MSC）联合利妥昔单抗（rituximab,美罗华）与甲强龙对系统性红斑狼疮（systemic lupus erythematosus,SLE）患者免疫炎性易栓状态的干预作用。方法8例SLE患者经肾活检确诊为狼疮性肾炎。予SLE活动指数（SLEDAI积分）评价病情活动程度;流式细胞术（FCM）监测B细胞清除、T细胞亚群及炎症介质表达水平;酶联免疫吸附法（ELISA）检测抗心磷脂抗体（ACA）、狼疮抗凝物（LA）水平;以磁珠法检测血凝常规、血浆D二聚体（D-D）、抗凝血酶（AT）等。结果随访第1个月临床症状明显改善,CD19和CD20降至＂0＂;至第3个月全组SLEDAI评分〈4分,Th1（IFN-γ）、Th2（IL-4）及CD11b、CD25水平均接近正常;随访至1年上述指标维持在正常值内。结论利妥昔单抗联合UC-MSC所具有的靶向作用,能有效清除外周血致病性B细胞,恢复Th1/Th2免疫平衡状态,减少炎症因子释放,促进机体免疫重建,恢复凝血-抗凝系统平衡,从而改善机体免疫炎性易栓状态。

The Therapeutic Role of Rituximab Combined with UC-MSC via Regulating Immune Hypercoagulable State on Patients with SLE

Objective To investigate the therapeutic role of rituximab combined with umbilical cord mesenchymal stem cells（ UC-MSC） on immune hypercoagulable state of the patients with systemic lupus erythematosus（ SLE）. Methods The eight patients with lupus nephritis（ LN） who were confirmed by biopsy.The degree of SLE severity was evaluated by the systemic lupus erythematosus disease activity index（ SLEDAI）. The level of B cell and T cell subsets were detected by flow cytometry（ FCM）. The level of ACA（ IgG/M/A）,LA and inflammatory factors in plasma was detected by enzyme-linked immunosorbent assay（ ELISA）. The level of D-D,AT-Ⅲ and conventional coagulation were detected by automatic coagulometer.Results After the treatment,the patients improved within 1 month. The percent of CD19 and CD20 reduced to 0. 00%. The SLEDAI of all patients were less than 4 after 3 months,the level of CD11b,CD25,Th1（ IFN-γ） and Th2（ IL-4） was significantly reduced. After one year,the level of CD19,CD20 and CD11b,CD25,Th1（ IFN-γ）,Th2（ IL-4） was within the normal range. Conclusion Rituximab combined with UC-MSC which is a targeted therapy to improve the immune hypercoagulable state by removing B cells,balancing the Th1 /Th2 and reducing the production of inflammatory cytokines.