Jiang Ying, Li Tai-sheng, Zhao Yan, Leng Xiao-mei, Zhang Xuan, Tang Fu-lin
Department of Rheumatology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2007 Jun;29(3):388-93.
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.
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 Sjögren'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 +), naïve T (CD4 + CD45RA), memory T (CD4 + CD45RO), and CD4/CD8 ratio.
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 naYve T cell percentage for a relatively long time.
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.
探讨重症/难治性自身免疫性疾病(AID)患者自体造血干细胞移植(HSCT)前后淋巴细胞亚群的动态变化,研究AID患者移植后的免疫重建情况。
选取2003年4月至2005年4月在北京协和医院登记行HSCT的13例重症/难治性AID患者,其中系统性红斑狼疮患者8例、类风湿关节炎患者4例、原发性干燥综合征(pSS)患者1例。在动员前/后、预处理前以及移植后2周、1个月、3个月、6个月、12个月和18个月采集血样。采用流式细胞术检测淋巴细胞亚群,包括T细胞(CD3 +)、B细胞(CD19 +)、自然杀伤细胞(CD3-CD16 + CD56 +)、辅助性T细胞(CD3 + CD4 +)、细胞毒性T细胞(CD3 + CD8 +)、初始T细胞(CD4 + CD45RA)、记忆T细胞(CD4 + CD45RO)以及CD4/CD8比值。
与正常或类风湿关节炎患者相比,系统性红斑狼疮患者的淋巴细胞亚群严重异常(均P < 0.01)。B细胞在18个月内恢复至正常水平,但自然杀伤细胞和T细胞仍维持在较低水平。辅助性T细胞和初始T细胞的重建延迟,导致CD4/CD8比值倒置以及初始T细胞百分比在较长时间内处于较低水平。
系统性红斑狼疮患者淋巴细胞亚群异常比类风湿关节炎患者更严重。尽管移植后移植物及患者体内大多数自身免疫性T/B细胞可被有效清除,但非清髓性预处理可能存在AID复发风险。CD4 + T细胞长期受抑制可能与移植后AID病情缓解有关。