Decreased neuronal inhibition in cerebral cortex in obsessive-compulsive disorder on transcranial magnetic stimulation
Decreased neuronal inhibition in cerebral cortex in obsessive-compulsive disorder on transcranial magnetic stimulation
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DOI：
10.1016/s0140-6736(05)60009-8
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发表时间：
1998-09-12
期刊：
影响因子：
168.9
通讯作者：
Wassermann, EM
中科院分区：
文献类型：
--
作者：
Greenberg, BD;Ziemann, U;Wassermann, EM
清髓性化疗后移植自体造血干细胞（HSC）已被提出作为一种潜在的治疗策略，严重和难治性自身免疫性疾病。[1]然而，在移植未分离的HSC后观察到疾病复发，可能是由于致病性T细胞的再输注。因此，自体HSC移植的T细胞耗竭目前被推荐用于自身免疫性疾病。这种移植的一个主要问题是免疫系统的恢复，特别是在成年人中。我们报告一位年轻女子成功地治疗自体造血干细胞移植类风湿性关节炎。一名患有难治性类风湿性关节炎的22岁白色女性患者，经医院伦理委员会批准并给予知情同意后，被选择进行自体HSC移植。外周血干细胞的动员是通过环磷酰胺（1.5 g/m2）和依托泊苷（300 mg/m2）实现的，随后给予粒细胞集落刺激因子（5 g/kg）。白细胞分离产物通过CD 34干细胞富集，并通过Isolex 300 i装置（巴克斯特免疫治疗部，Deerfield，USA）进一步去除CD 4和CD 8细胞。流式细胞术显示HSC移植物（6· 5106 CD 34细胞/kg，纯度为98· 4%）缺乏T细胞。根据共识指南，在1997年8月28日（第0天）进行T细胞去除的HSC移植，第7天至第4天每天给予白消安4 mg，第3天至第2天每天给予环磷酰胺60 mg。移植后310个月，患者无关节炎，健康评估问卷评分为1分（移植前为13分），血清C反应蛋白浓度低于2 mg/dL（移植前为12 mg/dL），未使用任何抗风湿药物。血液CD 4细胞计数恢复至移植前值（384/mm 3），CD 45 RA初始细胞再次出现（占总CD 4细胞的6.3%）。与移植后3个月观察到的主要偏移相比，表达不同V家族T细胞受体的CD 4 T细胞计数显示T细胞多样性恢复（表）。同样，体外T细胞对念珠菌素的增殖反应在3个月时大大受损，恢复到移植前水平
Transplantation of autologous haemopoietic stem cells (HSC) after myeloablative chemotherapy has been proposed as a potential therapeutic strategy for severe and refractory autoimmune diseases. 1 Disease recurrence has, however, been seen after transplantation of unseparated HSC, presumably because of reinfusion of pathogenic T cells. 2 T-cell depletion of the autologous HSC transplant is, therefore, currently recommended for autoimmune disease. 3 A major concern with such transplants is the restoration of the immune system, especially in adults. We report on a young woman successfully treated by autologous HSC transplantation for rheumatoid arthritis. A white woman aged 22 years who had intractable rheumatoid arthritis refractory to available antirheumatic agents was selected for autologous HSC transplantation after approval by the ethics committee of the hospital and after she gave informed consent. Mobilisation of peripheral-blood stem cells was achieved with cyclophosphamide (1· 5 g/m2) and etoposide (300 mg/m2), followed by granulocyte colony-stimulating factor administration (5 g/kg). The leukapheresis product was enriched by CD34 stem cells and further depleted of CD4 and CD8 cells by Isolex 300i device (Baxter Immunotherapy Division, Deerfield, USA). The HSC transplant (6· 5106 CD34 cells/kg with a purity of 98· 4%) was shown to be devoid of T cells by flow cytometry. Transplantation of T-cell-depleted HSC was performed on Aug 28, 1997 (day 0), after administration of busulfan 4 mg daily from day 7 to day 4 and cyclophosphamide 60 mg daily from day 3 to day 2, according to consensus guidelines. 310 months after transplantation, the patient was free of arthritis, with a health-assessment questionnaire score of 1 (compared with 13 before transplantation) and a serum concentration of C-reactive protein of less than 2 mg/dL (value before transplantation 12 mg/dL) without any antirheumatic medication. Blood CD4 cell count returned to pretransplantation values (384/mm3), and CD45 RA naive cells reappeared (6· 3% of total CD4 cells). Enumeration of CD4 T cells expressing T-cell receptors of different V families showed a restoration of T-cell diversity, compared with the major skewing seen 3 months after transplantation (table). Similarly, the in-vitro T-cell proliferative responses to candidin which was greatly impaired at 3 months, returned to pretransplantation levels