中国医学科学院学报

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中国医学科学院学报

中国医学科学院学报 ›› 2007, Vol. 29 ›› Issue (3): 388-393.

• 论著 • 上一篇    下一篇

自体造血干细胞移植治疗重症/难治性自身免疫病的淋巴细胞亚群演变

蒋 颖1,李太生2,赵 岩1,冷晓梅1,张 烜1,唐福林1   

  1. 中国医学科学院 北京协和医学院 北京协和医院 1风湿免疫科 2感染科,北京 100730
  • 收稿日期:2007-03-23 修回日期:1900-01-01 出版日期:2007-06-30 发布日期:2007-06-30
  • 通讯作者: 李太生

Changes of Lymphocyte Subsets in Autologous Hemopoietic Stem Cell Transplantation for Severe/refractory Autoimmune Disease

JIANG Ying1,LI Tai-sheng2,ZHAO Yan1,LENG Xiao-mei1, ZHANG Xuan1,TANG Fu-lin1   

  1. 1 Department of Rheumatology, 2 Department of Infectious Diseases, PUMC Hospital, CAMS and PUMC, Beijing 100730, China
  • Received:2007-03-23 Revised:1900-01-01 Online:2007-06-30 Published:2007-06-30
  • Contact: LI Tai-sheng

摘要: 摘要:目的 研究自体造血干细胞移植(HSCT)治疗重症/难治性自身免疫病(AID )的淋巴细胞亚群免疫重建规律。方法 以2003年4月~2005年4月在我院行HSCT的13例AID患者和40例正常对照者为研究对象,采用流式细胞学技术分别于动员前、后,移植后2周,1、3、6、12及18个月共8个时间窗监测受试者体内的淋巴细胞、T细胞(CD3+)、B细胞(CD19+)、NK细胞 (CD3-CD16+CD56+)、Th细胞(CD3+CD4+)、Tc细胞(CD3+CD8+)、纯真T细胞(CD4+CD45RA)、记忆 T 细胞(CD4+CD45RO)和CD4/CD8比值的变化。结果 13例AID患者中,系统性红斑狼疮(SLE)8例,类风湿关节炎(RA)4例,原发性干燥综合征(pSS)1例。动员前SLE组的淋巴细胞各亚群均明显低于正常人和RA组 (P均<0.01)。B细胞在移植后18个月内从0恢复至正常。NK细胞和T细胞亚群未恢复至正常,NK细胞恢复较快,维持低水平; T细胞亚群中的CD4+T细胞恢复迟于CD8+T细胞, 纯真T细胞恢复迟于记忆T细胞。结论 SLE患者外周血中淋巴细胞、T细胞及各亚群、B细胞、NK细胞异常较RA患者更明显。AID患者体内和移植物的T/B细胞去除有效,非清髓性处理可能成为AID复发隐患,CD4+T细胞的长期受抑可能与AID患者移植后病情缓解相关。

关键词: 自体造血干细胞移植, 自身免疫病, 淋巴细胞亚群

Abstract: ABSTRACT:Objective To investigate the dynamic changes of lymphocyte subsets before and after autologous hemopoietic stem cell transplantation (HSCT) in severe/refractory autoimmune disease (AID) and study the post-transplantation immunological reconstitution in AID. Methods Thirteen patients with severe/refractory AID who registered for HSCT from April 2003 to April 2005 in Peking Union Medical College Hospital, including 8 patients with systemic lupus erythematosus, 4 patients with rheumatoid arthritis, and 1 patient with primary Sjgrens syndrome(pSS) were enrolled in this study. Blood samples were collected before/after mobilization, before conditioning, and 2 weeks, 1 month, 3 months, 6 months, 12 months, and 18 months post-transplantation. Lymphocyte subsets were tested by flow cytometry as follows: T cell (CD3+), B cell (CD19+), natural killer (CD3-CD16+CD56+), Th(CD3+CD4+), Tc(CD3+CD8+), nave T(CD4+CD45RA), memory T(CD4+CD45RO), and CD4/CD8 ratio. Results Lymphocyte subsets for SLE patients were severely abnormal compared to normal or RA patients (both P<0.01). B cell reconstituted to normal level within 18 months, meanwhile NK and T cell remained low. The repopulations of Th and nave T cell were delayed, which caused the up-side-down of CD4/CD8 ratio and low level of nave T cell percentage for a relatively long time. Conclusions Lymphocyte subsets abnormality in SLE patients are more severe than in RA patients. Although most autoimmune T/B cell in the grafts and patients can be effectively removed after transplantation, nonmyeloablative conditioning may be a risk for the relapse of AID. The long-term inhibition of CD4+ T cell may be related with the relief of AID after transplantation.

Key words: autolocous dematopoietic stem cell transplantation, autoimmune disease, lympdocyte subset