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

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

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。

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 Sjogren＇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＇fve T （CD4 ＋ CD45 RA） , memory T （ CD4 ＋ CD45 RO） , 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 naive T cell were delayed, which caused the up-side-down of CD4/CD8 ratio and low level of naive 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.