Institute for Inflammation Research, Center for Rheumatology and Spine Disease, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark; Haematopoietic Cell Transplantation and Primary Immune Deficiency, Department of Paediatric and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
Institute for Inflammation Research, Center for Rheumatology and Spine Disease, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark; The Tissue Typing Laboratory, Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark.
Clin Immunol. 2018 Feb;187:26-32. doi: 10.1016/j.clim.2017.08.015. Epub 2017 Aug 31.
Interleukin-7 is a cytokine essential for T cell homeostasis. IL-7 binds to cellular IL-7 receptors in competition with a soluble form of the receptor (sIL-7Rα). We hypothesized that altered sIL-7Rα levels may cause adverse outcomes in patients undergoing HSCT. In parallel, we investigated the impact of the IL-7Rα SNP rs6897932, which has been associated with release of IL-7R. The sIL-7Rα levels decreased during HSCT (from 114ng/ml before to 48ng/ml at day +14 (P<0.0001)). This pattern was inversely mirrored by IL-7. The IL-7/sIL-7Rα ratio at day +14 was significantly higher in patients developing grades II-IV aGVHD (OR=4.3, P=0.026). Furthermore, donor carriage of the rs6897932 T allele was associated with reduced sIL-7Rα levels, increased risk of grades II-IV aGVHD (OR=2.4, P=0.055) and increased transplant-related mortality (CC=4.5%, CT=21.4% and TT=27.3%, P=0.0037). In conclusion, this study suggests an impact of sIL-7Rα levels and rs6897932 donor genotype on alloreactivity and outcome after HSCT.
白细胞介素-7 是 T 细胞稳态所必需的细胞因子。IL-7 与细胞 IL-7 受体结合，与受体的可溶性形式（sIL-7Rα）竞争。我们假设改变 sIL-7Rα 水平可能导致接受 HSCT 的患者出现不良后果。同时，我们研究了与 IL-7R 释放相关的 IL-7Rα SNP rs6897932 的影响。sIL-7Rα 水平在 HSCT 期间下降（从移植前的 114ng/ml 降至第 +14 天的 48ng/ml（P<0.0001））。这种模式与 IL-7 相反。第 +14 天发生 II-IV 度急性移植物抗宿主病（aGVHD）的患者的 IL-7/sIL-7Rα 比值显著更高（OR=4.3，P=0.026）。此外，供体携带 rs6897932 T 等位基因与 sIL-7Rα 水平降低、II-IV 度 aGVHD 的风险增加（OR=2.4，P=0.055）和移植相关死亡率增加相关（CC=4.5%，CT=21.4%和 TT=27.3%，P=0.0037）。总之，这项研究表明 sIL-7Rα 水平和 rs6897932 供体基因型对 HSCT 后同种异体反应性和结果有影响。
