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自体 PBSC 移植后无体外移植物处理治疗难治性系统性红斑狼疮的免疫恢复。

Immune recovery after autologous PBSC transplantation without in vitro graft manipulation for refractory systemic lupus erythematosus.

机构信息

Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

出版信息

Bone Marrow Transplant. 2011 Nov;46(11):1450-4. doi: 10.1038/bmt.2010.332. Epub 2011 Jan 17.

Abstract

Autologous hematopoietic SCT (ASCT) has been investigated as salvage therapy for refractory systemic lupus erythematosus (SLE). Although immune recovery after ASCT with in vitro purging of lymphocytes has been extensively studied, little information is available about immune recovery after ASCT without in vitro purging. Therefore, we analyzed the immune recovery of a patient who successfully underwent ASCT without in vitro purging for refractory SLE. In addition to the numbers of PBL subsets, T-cell receptor rearrangement excision circles (TRECs) and the T-cell receptor repertoire diversity of both CD4+ and CD8+ T cells were sequentially analyzed. All SLE-related symptoms disappeared within 3 months after ASCT and the serum anti-dsDNA Ab became undetectable. The number of CD4+CD45RO+ memory T cells remained lower than that in healthy adult controls, but the number of CD4+CD45RA+ naïve T cells showed a rapid increase after ASCT. TRECs of both CD4+ and CD8+ T cells were strongly suppressed before ASCT, but consistently increased after ASCT. The T-cell receptor repertoire of CD8+ T cells was skewed before ASCT, but the diversity recovered after ASCT. ASCT with the reinfusion of a large number of autologous T cells did not impair the recovery of naive T cells or resetting of the immune system.

摘要

自体造血干细胞移植(ASCT)已被研究作为难治性系统性红斑狼疮(SLE)的挽救性治疗。虽然已经广泛研究了 ASCT 后体外清除淋巴细胞后的免疫恢复情况,但关于 ASCT 后没有体外清除时的免疫恢复情况知之甚少。因此,我们分析了一位成功接受 ASCT 治疗难治性 SLE 而未进行体外清除的患者的免疫恢复情况。除了 PBL 亚群的数量外,还依次分析了 CD4+和 CD8+T 细胞的 T 细胞受体重排切除环(TRECs)和 T 细胞受体多样性。ASCT 后 3 个月内所有 SLE 相关症状消失,血清抗 dsDNA Ab 变为不可检测。CD4+CD45RO+记忆 T 细胞的数量仍低于健康成人对照,但 ASCT 后 CD4+CD45RA+幼稚 T 细胞的数量迅速增加。ASCT 前 CD4+和 CD8+T 细胞的 TRECs 受到强烈抑制,但 ASCT 后持续增加。ASCT 前 CD8+T 细胞的 T 细胞受体谱发生偏斜,但 ASCT 后恢复了多样性。ASCT 伴随着大量自体 T 细胞的再输注,并未损害幼稚 T 细胞的恢复或免疫系统的重置。

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