全相合异基因造血干细胞移植后免疫重建的研究

doi:10.3969/j.issn.1673-8640.2014.09.013

摘要/Abstract

摘要： 目的探讨人类白细胞抗原(HLA)全相合异基因造血干细胞移植(allo-HSCT)后免疫重建的规律。方法选择42例2009至2013年在瑞金医院血液科骨髓移植病区接受allo-HSCT患者,采用速率散射比浊法检测预处理前和移植后1、3、6、12及24个月的血清免疫球蛋白IgG、IgA、IgM及IgE水平,流式细胞术(FCM)检测预处理前,移植日,移植后14、21 d和1、3、6、12、18及24个月的T淋巴细胞(CD3⁺、CD3⁺CD4⁺、CD3⁺CD8⁺)、B细胞(CD19⁺)及自然杀伤(NK)细胞(CD56⁺CD16⁺),总结移植后免疫球蛋白及各淋巴细胞亚群的恢复情况并对影响免疫重建的因素进行探讨。结果 CD3⁺及CD3⁺CD8⁺T细胞移植后14 d开始恢复正常,CD3⁺CD4⁺T细胞恢复缓慢,在术后2年内低于或接近正常水平。CD56⁺CD16⁺细胞移植后恢复较快,21 d左右开始恢复正常水平。CD19⁺细胞在移植后6个月左右恢复正常,免疫球蛋白IgM、IgG、IgA恢复正常的时间分别为1、3及6个月。不同性别患者移植后免疫重建无明显差异,供体来自同胞的患者免疫重建速度较非血缘移植快。发生严重感染及Ⅲ～Ⅳ移植物抗宿主病(GVHD)患者CD3⁺CD8⁺T细胞水平移植后早期明显高于未发生GVHD及感染者。发生Ⅲ～ⅣGVHD患者移植后早期CD3⁺细胞明显高于未发生GVHD患者,并且CD3⁺CD4⁺T细胞恢复有延迟趋势。结论 allo-HSCT后淋巴细胞亚群的免疫重建顺序依次是:CD56⁺CD16⁺,CD3⁺CD8⁺,CD19⁺及CD3⁺CD4⁺。HLA全相合有利于免疫重建,移植治疗中抗胸腺球蛋白的应用、移植后GVHD发生等是影响免疫重建的最重要因素。

关键词: 免疫重建, 异基因造血干细胞移植, 淋巴细胞

Abstract: Objective To investigate the immune reconstitution after human leukocyte antigen (HLA)-matched allogenetic hematopoietic stem cell transplantation (allo-HSCT). Methods A total of 42 patients undergoing allo-HSCT from 2009 to 2013 in the Blood and Marrow Transplantation Center, Department of Hematology, Ruijin Hospital were enrolled in this study. The immunoglobulin levels of IgG, IgA, IgM and IgE prior to preconditioning and at 1, 3, 6, 12 and 24 months after transplantation were determined by rate nephelometry. T lymphocytes (CD3⁺, CD3⁺CD4⁺ and CD3⁺CD8⁺), B cell (CD19⁺) and natural killer (NK) cell (CD56⁺CD16⁺) levels were determined by flow cytometry(FCM) prior to preconditioning, at the day of transplantation, 14 and 21 d, 1, 3, 6, 12, 18 and 24 months after transplantation. The recovery of immunoglobulin and lymphocyte subsets was analyzed, and the impacts of pre-and post-transplantation variables were evaluated. Results The levels of CD3⁺ and CD3⁺CD8⁺ returned to be normal at 14 d after transplantation, while the recovery of CD3⁺CD4⁺ was slow, and its level remained lower than or closer to be normal in 2 years after transplantation. CD56⁺CD16⁺ recovered rapidly and returned to be normal at approximately 21 d after transplantation. CD19⁺ were back to be normal at 6 months after transplantation, and the recovery times of IgM, IgG and IgA were 1, 3 and 6 months, respectively. No significant differences were found in the immune reconstitution between male and female patients. The immune reconstitution of sibling donor transplantation was faster than that of unrelated donor transplantation. The levels of CD3⁺CD8⁺ at early stage of post-transplantation were significantly higher in patients with severe infection and Ⅲ-Ⅳ graft-versus-host disease (GVHD) than those in patients without infection and GVHD. For patients with Ⅲ-Ⅳ GVHD, CD3⁺ was significantly higher than that for patients without GVHD at early stage of post-transplantation, while the recovery of CD3⁺CD4⁺ tended to be slow. Conclusions The lymphocyte subsets recover after allo-HSCT in the following order: CD56⁺CD16⁺, CD3⁺CD8⁺, CD19⁺ and CD3⁺CD4⁺. HLA matching benefits the immune reconstitution. The application of anti-thymocyte globulin and GVHD occurrence after transplantation are the most important factors influencing the immune reconstitution.

Key words: Immune reconstitution, Allogenetic hematopoietic stem cell transplantation, Lymphocyte

中图分类号:

R446.61

卫蓓文,唐暐,彭奕冰,胡炯. 全相合异基因造血干细胞移植后免疫重建的研究[J]. 检验医学, 2014, 29(9): 925-930.

WEI Beiwen, TANG Wei, PENG Yibing, HU Jiong. The study of immune reconstitution after human leukocyte antigen-matched allogenetic hematopoietic stem cell transplantation[J]. , 2014, 29(9): 925-930.

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