Kielsen K, Jordan K K, Uhlving H H, Pontoppidan P L, Shamim Z, Ifversen M, Heilmann C, Nielsen C H, Sengeløv H, Ryder L P, Müller K G
Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Scand J Immunol. 2015 Jan;81(1):72-80. doi: 10.1111/sji.12244.
Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We prospectively measured IL-7 levels in 81 patients undergoing myeloablative HSCT with either sibling donor or an unrelated donor. Plasma IL-7 levels peaked at day +7 post-transplant (1.3-82.4 pg/ml), at the time of maximal lymphopaenia. In multivariate analysis, peak levels of IL-7 were significantly higher in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4(+) : β = -2.1 × 10(6) cells/l, P = 0.062) in multivariate analyses. In adults, high IL-7 levels were associated with increased risk of grade II-IV aGVHD (OR = 5.4, P = 0.036) and reduced overall survival (P = 0.046). The present data indicate that high plasma levels of IL-7 in the early post-transplant period are predictive for slow T cell reconstitution, increased risk of aGVHD and increased mortality following HSCT.
感染和急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（HSCT）后与治疗相关的死亡率和发病率的主要原因。这两种并发症都依赖于基于供体T细胞的T淋巴细胞群体的重建。虽然白细胞介素-7（IL-7）是胸腺中T细胞从头发育和T细胞稳态外周扩增所必需的细胞因子这一点已得到充分证实，但之前尚未研究过HSCT后循环IL-7水平与T细胞重建之间的关联。我们前瞻性地测量了81例接受清髓性HSCT的患者的IL-7水平，这些患者的供体为同胞或无关供体。血浆IL-7水平在移植后第7天达到峰值（1.3 - 82.4 pg/ml），此时淋巴细胞减少最为严重。在多变量分析中，与未接受抗胸腺细胞球蛋白（ATG）治疗的患者相比，接受ATG治疗的患者IL-7峰值水平显著更高（P = 0.0079）。移植后第7天的IL-7水平与移植后第30至60天的T细胞计数呈负相关（移植后第60天：CD3(+)：β = -10.6×10⁶细胞/升，P = 0.0030；CD8(+)：β = -8.4×10⁶细胞/升，P = 0.061；CD4(+)：β = -2.1×10⁶细胞/升，P = 0.062）。在成人中，高IL-7水平与II - IV级aGVHD风险增加（OR = 5.4，P = 0.036）和总生存率降低（P = 0.046）相关。目前的数据表明，移植后早期血浆中高IL-7水平可预测HSCT后T细胞重建缓慢、aGVHD风险增加和死亡率增加。
