鼠抗人CD_3T淋巴细胞单克隆抗体治疗再生障碍性贫血免疫调节作用的临床观察  

Murine anti-human CD_3 T lymphocyte monoclonal antibody in aplastic anemia

作　　者：李丽珍[1] 宋强[1] 赵川莉[1] 吴新春[2] 郭成山[2] 王鲁群[1] 

机构地区：[1]山东大学齐鲁医院血液学研究室,山东济南250012 [2]山东大学第二医院血液科,山东济南250033

出　　处：《山东大学学报（医学版）》2005年第9期809-813,共5页Journal of Shandong University:Health Sciences

摘　　要：目的:探讨特异性细胞免疫抑制剂鼠抗人CD3T淋巴细胞单克隆抗体(CD3单抗)治疗再生障碍性贫血(再障,AA)的机制及疗效。方法:22例AA患者中位年龄26岁,其中重型再障(SAA)15例,慢性再障(CAA)7例。既往未经特殊治疗12例,既往治疗无效的10例中,已加用环孢素(CsA)≥3个月7例。CD3单抗给药方法:5mg静脉滴注,每天1次,连用10d为1疗程。采用APAAP法测定T细胞表面抗原的表达;应用ELISA法测定外周血单个核细胞培养上清中细胞因子的含量。结果:随访3～22个月,有17例骨髓象明显好转,外周血白细胞平均升高1.61×109/L,中性粒细胞升高0.77×109/L,血红蛋白升高42g/L,血小板升高45×109/L(!均<0.01)。其中,6例基本治愈,7例缓解,4例明显进步,总有效率为77.27%,5例无效;T淋巴细胞亚群的变化:CD4/CD8比值由1.20±0.41上升至1.44±0.39、HLA-DR的表达率由(32.1±14.7)%下降至(14.6±5.3)%(!均<0.01);体外培养患者外周血单个核细胞分泌下列淋巴因子含量的中位数值(U/ml):肿瘤坏死因子α(TNFα)、干扰素γ(IFNγ)与白细胞介素-2(IL-2)分别由252、796和94降至146、524和48(!均<0.01)。不良反应:单抗治疗期间,全部病例均发热,6例出现胸闷、呼吸困难,但治疗期间无1例死亡。结论:与其他常用的免疫抑制剂相比,CD3单抗治疗AA疗效快、有效率高且安全性较好,其免疫调节作用特异性强。Objective： To investigate the efficacy and mechanism of specific murine anti-human CD3 T lymphocyte monoclonal antibody （CD3 McAb） for aplastic anemia （AA）. Methods： Twenty-two AA patients whose median age was 26 years, including 12 untreated patients and 10 non-responding ones to ever management, were administrated of 5mg anti-CD3 McAb per day for total 10 days. T lymphocyte antigens were detected by APAAP method and lymphokine levels were detected by ELISA method. Results： The response rate was 77.27% of the 17 patients （17/22）, six were cured and seven achieved partial remission after following-up for 3 to 22 months. As total contrast to pretreatment, the proliferation of bone marrows of 17 cases grew better; the leukocytes, granulocytes, hemoglobin and platelets of peripheral blood increased 1.61× 10^9/L,0.77× 10^9/L,42 g/L and 45× 10^9/L respectively （P〈0.01）; CD4/CD8 ratio of T cell subsets increased from 1.20±0.41 to 1.44±0.39, while the expression of HLA-DR antigen decreased from （32.1±14.7）% to （14.6±5.3） % respectively （P〈0.01）; TNFα, IFNγ and IL-2 secreted by peripheral blood mononuclear cells （PBMNCs） decreased from 252, 796 and 94 to 146, 524 and 48U/ml on the medium respectively （P〈0.01）. All patients had fever, 6 had short of breath, but none died during the treatment. Conclusion： Contrasted with other kinds of common immune suppressors, CD3 McAb shows sooner response and probably higher efficacy and safety for AA patients, and it has higher specificity in regulating immune response.

关 键 词：抗体 单克隆 T淋巴细胞 CD3 贫血 再生障碍性 淋巴因子 

分 类 号：R556.5[医药卫生—血液循环系统疾病]