IL-27在无关供体异基因造血干细胞移植中对移植物抗宿主病的作用

Interleukin-27：a biomarker for prediction of acute graft-versus-host disease after allogeneic hemato-poietic stem cell transplantation from unrelated donors

目的 检测血清白细胞介素-27（IL-27）在无关供体异基因造血干细胞移植（allo-HSCT）中对急性移植物抗宿主病（aGVHD）的预测价值.方法 收集2012年1月至2012年12月72例无关供体allo-HSCT患者血清,同时收集2013年70例无关供体allo-HSCT患者血清进行结果验证.所有患者均采用清髓性预处理方案,环孢素A（CsA）＋霉酚酸酯（MMF）＋ 短程甲氨蝶蛉（MTX）预防移植物抗宿主病（GVHD）.通过ELISA试剂盒检测血清中IL-27的表达水平.我们回顾性地评估IL-27指数,定义为中性粒细胞植入日IL-27表达水平与预处理前水平的比值,对aGVHD的预测价值.结果 Ⅱ-Ⅳ度aGVHD患者血清IL-27指数明显降低（0 -Ⅰ度：1.89 ±0.68 vs Ⅱ-Ⅳ度：1.26 ± 0.49;P〈0.0001）.IL-27指数对Ⅱ-Ⅳ度 aGVHD有较好的预测价值（AUC=0.782,95% CI：0.675-0.889,P〈0.001）.IL-27指数〈1.33更易发生Ⅱ-Ⅳ度aGVHD （P〈0.001）.多因素分析证实IL-27指数〈1.33是Ⅱ-Ⅳ度aGVHD最强的危险因素（HR=4.50, 95% CI： 2.1 -9.8, P〈0.01）.在2013年患者血清中同样证实了此发现.结论 低表达IL-27指数可以预测无关供体移植后患者Ⅱ-Ⅳ度aGVHD的发病率.

Objective To analyze the predictive value of serum interleukin-27 （IL-27） for acute graft-versus-host disease （aGVHD） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） from unrelated donors. Methods Serum samples were collected from 72 patients after receiving allo-HSCT from unrelated donors during January to December 2012. Serum samples collected from 70 patients received allo-HSCT in 2013 were used for confirmation. All patients received myeloablative conditioning regimen prior to allo-HSCT. Cyclosporin A （CsA）＋mycophenolate mofetil （MMF）＋short-term methotrexate （MTX） were used for GVHD prophylaxis. Serum IL-27 levels in patients with aGVHD were measured by ELISA. The pre-dictive value of IL-27 index,defined as the ratio of serum IL-27 level at neutrophil engraftment to that before pre-conditioning regimen, for allogeneic HSCT was retrospectively analyzed. Results Serum IL-27 index was significantly decreased in patients with gradeⅡ-ⅣaGVHD（grade 0-Ⅰ ： 1.89±0.68 vs gradeⅡ-Ⅳ ：1.26±0.49;P〈0.000 1）. IL-27 index had good value for grade Ⅱ-Ⅳ aGVHD （AUC=0.782,95% CI：0.675-0.889,P〈0.001）. Patients with a lower serum IL-27 index （〈1.33） were more likely to have a higher cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with a higher serum IL-27 index （P〈0.001）. Multivariate analysis confirmed that low IL-27 index was the most significant risk factor for gradeⅡ-Ⅳ aGVHD （HR=4.50,95% CI：2.1-9.8,P〈0.01）. These findings were consistent with the results found in the serum samples collected in 2013. Conclusion Low IL-27 index could be used to predict the incidence of grade Ⅱ-Ⅳ acute GVHD after allo-HSCT from unrelated donors.