异基因造血干细胞移植后共刺激分子LIGHT/HVEM的表达与GVHD的关系

目的 探讨异基因造血干细胞移植(allo-HSCT)后共刺激分子LIGHT和HVEM的表达与移植物抗宿主病(GVHD)发生的关系.方法 26例allo-HSCT患者中,预处理方案采用环磷酰胺+足叶乙甙+全身照射11例,采用氟达拉滨+阿糖胞苷+白消安12例,采用环磷酰胺3例.移植时,输注单个核细胞(5.89±3.36)×10~8/kg,CD34~+细胞(3.29±1.29)×10~6/kg.预防急性GVHD(aGVHD)的方案采用环孢素A+短程甲氨蝶呤+吗替麦考酚酯,HLA半相合及非血缘关系者加用抗胸腺细胞球蛋白.GVHD的诊断与分级采用西雅图标准.在预处理前、移植后15 d、发生aGVHD时及aGVHD经治疗好转后分别采集患者外周血2 ml,采用三色流式细胞术进行检测,同时以15名健康志愿者的血液标本作为正常对照.结果 所有患者均获得造血功能重建,移植物均完全植活.移植后共发生aGVHD9例,发生率为35%,其中Ⅲ～Ⅳ度者3例,8例经治疗后好转,1例治疗无效死亡;发生慢性GVHD(cGVHD)7例,发生率为26.9%.患者预处理前和移植后15 d及正常人外周血T淋巴细胞几乎不表达LIGHT,组成性表达HVEM;发生GVHD时,LIGHT表达显著上调,HVEM表达下调;GVHD好转后,LIGHT和HVEM的表达恢复正常.移植后15 d时,发生aGVHD者LIGHT的表达高于未发生aGVHD者,而HVEM的表达较低(P<0.05).Ⅲ～Ⅳ度aGVHD者LIGHT的表达明显高于Ⅰ～Ⅱ度者(P<0.05).结论 LIGHT/HVEM在allo-HSCT后GVHD的发生和发展过程中起重要作用,通过监测该共刺激分子的表达对aGVHD的发生有一定预示作用.

The expression of LIGHT and HVEM in T lymphocytes post allo-HSCT and its relation to the development of GVHD

Objective To explore the relationship between the expression of LIGHT/HVEM in patients after allo-HSCT and the development of GVHD. Methods The expression of LIGHT and HVEM in T lymphocytes was detected by FACS Calibur. Results All patients achieved engraftment and hematopoiesis reconstitution, aGVHD occurred in 9 of 26 patients (34.6%) with grade Ⅲ-Ⅳ aGVHD in 3 cases. Seven cases developed cGVHD (26.9%). LIGHT was not expressed in T lymphocytes from healthy donors and patients without GVHD, while constitutive expression of HVEM was detected. When aGVHD occurred, the expression levels of LIGHT in T lymphocytes were significantly increased, while those of HVEM decreased. After GVHD was controlled, the expression levels of those co-stimulators went back to normal On the day 15 after transplantation, the expression of LIGHT in T lymphocytes of patients with aGVHD later was significantly higher, while that of HVEM lower than in those without aGVHD. The patients with aGVHD of grades Ⅲ-Ⅳ demonstrated higher LIGHT expression than in those with aGVHD of grades Ⅰ-Ⅱ. Conclusion The expression of LIGHT and HVEM might be involved in the development of GVHD after allo-HSCT and could be used as one of the useful indicators in predicting aGVHD.