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经减强度预处理的异基因造血干细胞移植后 IL-7 和 IL-15 的血浆水平与急性移植物抗宿主病的关系。

Plasma levels of IL-7 and IL-15 after reduced intensity conditioned allo-SCT and relationship to acute GVHD.

机构信息

Université Lille Nord de France, Lille, France.

出版信息

Bone Marrow Transplant. 2011 Oct;46(10):1374-81. doi: 10.1038/bmt.2010.300. Epub 2010 Dec 6.

Abstract

To assess the impact of homeostatic expansion on the occurrence of acute GVHD after reduced intensity conditioning (RIC) transplantation, systemic levels of IL-7 and IL-15 and expression of their specific receptor chains were prospectively investigated in 45 fully HLA-matched allograft recipients. IL-7 and IL-15 levels peaked at four- to fivefold over pre-conditioning values. IL-7 levels were inversely correlated to absolute T-cell counts. Peak IL-15 levels positively correlated to concurrent CRP levels, but normalized earlier than IL-7. These results indicate that the kinetic course of IL-7 depends mainly on initiation of T-cell recovery, while IL-15 depends more on peri-transplant inflammation after RIC. Longer duration of the rise in IL-7 levels was associated with preservation of a normal CD4/CD8 ratio. In all, 16 (35%) patients developed grade 2-4 acute GVHD at a median of 42 days post graft, preceded by higher IL-7 levels and more downregulation of IL-7 receptor α chain on CD4(+) T cells than in patients without acute GVHD, suggesting enhanced homeostatic expansion. In multivariate analysis, IL-7 level measured on day +30 was the foremost predictive factor for grade 2-4 acute GVHD (P=0.002). Measurement of IL-7 level after RIC transplantation might help predict risk of subsequent acute GvHD.

摘要

为了评估在经过低强度预处理(RIC)的移植后,体内平衡扩张对急性移植物抗宿主病(GVHD)发生的影响,我们前瞻性地研究了 45 名完全 HLA 匹配同种异体移植受者体内的 IL-7 和 IL-15 及其特异性受体链的系统水平。IL-7 和 IL-15 的水平在预处理值的四到五倍处达到峰值。IL-7 的水平与绝对 T 细胞计数呈负相关。峰值 IL-15 水平与同期 CRP 水平呈正相关,但比 IL-7 更早恢复正常。这些结果表明,IL-7 的动力学过程主要取决于 T 细胞恢复的启动,而 IL-15 更多地依赖于 RIC 后的移植期炎症。IL-7 水平升高持续时间较长与维持正常 CD4/CD8 比值有关。总共有 16 名(35%)患者在移植后中位数为 42 天出现 2-4 级急性 GVHD,其 IL-7 水平较高,CD4+T 细胞上的 IL-7 受体α链下调更为明显,表明体内平衡扩张增强。在多变量分析中,第 30 天测量的 IL-7 水平是 2-4 级急性 GVHD 的首要预测因素(P=0.002)。RIC 移植后 IL-7 水平的测量可能有助于预测随后发生急性 GvHD 的风险。

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