Association of Serum Interleukin-7 Levels With the Development of Acute Graft-Versus-Host Disease
Association of Serum Interleukin-7 Levels With the Development of Acute Graft-Versus-Host Disease
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DOI：
10.1200/jco.2008.17.1314
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发表时间：
2008-12-10
影响因子：
45.3
通讯作者：
Bishop, Michael R.
中科院分区：
文献类型：
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作者：
Dean, Robert M.;Fry, Terry;Bishop, Michael R.
目的急性移植物抗宿主病（GVHD）的发病率限制了同种异体造血干细胞移植（HSCT）治疗恶性肿瘤的成功。白介素 7 (IL-7) 是 T 细胞的主要稳态细胞因子，是小鼠模型中急性 GVHD 所必需的。与炎性细胞因子（例如 IL-2、肿瘤坏死因子 α）相比，IL-7 尚未在临床移植环境中对其与急性 GVHD 的关系进行广泛研究。患者和方法我们评估了 31 名患者的血清 IL-7 水平与急性 GVHD 的关联，这些患者在一项前瞻性临床试验中均接受降低强度同种异体治疗 来自人类白细胞抗原相同兄弟姐妹的 HSCT。 GVHD 预防包括环孢素和甲氨蝶呤。在入组时、移植当天、同种异体移植物输注前以及移植后 12 个月内按指定时间间隔测定血清 IL-7 水平和淋巴细胞群。 结果如预期，IL-7 水平与 T 细胞群呈负相关 (P < .00001)。急性 GVHD 与移植后第 +7 天 (P = .01) 和第 +14 天 (P = .00003) 较高的 IL-7 水平以及同种异体移植 CD34(+) 细胞剂量 (P = .01) 显着相关。第 +14 天的 IL-7 水平也与急性 GVHD 的严重程度相关 (P < .0001)。在逻辑回归模型中，这些因素对于分类患者是否发生急性 GVHD 具有高度敏感性（高达 86%）和特异性（100%）。 结论 这些数据支持临床前观察结果，即 IL-7 在诱发急性 GVHD 中发挥着关键作用，并为通过调节 IL-7 途径预防和治疗急性 GVHD 的新方法提供了合理的基础。
PurposeMorbidity from acute graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic stem-cell transplantation (HSCT) to treat malignancy. Interleukin-7 (IL-7), the principal homeostatic cytokine for T cells, is required for acute GVHD in murine models. In contrast to inflammatory cytokines (eg, IL-2, tumor necrosis factor alpha), IL-7 has not been studied extensively in the clinical transplant setting relative to its relationship with acute GVHD.Patients and MethodsWe evaluated the association of serum IL-7 levels with acute GVHD in 31 patients who were uniformly treated in a prospective clinical trial with reduced-intensity allogeneic HSCT from human leukocyte antigen-identical siblings. GVHD prophylaxis consisted of cyclosporine and methotrexate. Serum IL-7 levels and lymphocyte populations were determined at enrollment, the day of transplantation before the allograft infusion, and at specified intervals through 12 months post-transplantation.ResultsAs expected, IL-7 levels were inversely correlated with T-cell populations (P < .00001). Acute GVHD was significantly associated with higher IL-7 levels at day +7 (P = .01) and day +14 (P = .00003) post-transplantation as well as with the allograft CD34(+) cell dose (P = .01). IL-7 levels at day +14 also correlated with the severity of acute GVHD (P < .0001). In logistic regression models, these factors were highly sensitive (up to 86%) and specific (100%) for classifying whether patients developed acute GVHD.ConclusionThese data support preclinical observations that IL-7 plays a critical role in inducing acute GVHD and provide a rational basis for novel approaches to prevent and treat acute GVHD through modulation of the IL-7 pathway.