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

作　　者：刘霜竹 韩晶晶 龚欢乐[2] 戚嘉乾 刘红 陈佳[1,3] 马守宝 吴德沛[1,2,3] Liu Shuangzhu;Han Jingjing;Gong Huanle;Qi Jiaqian;Liu Hong;Chen Jia;Ma Shoubao;Wu Depei(Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China;Institute of Blood and Marrow Transplantation, Soochow University, Suzhou 215213, China;Collaborative Innovation Center of Hematology, Soochow University, Key laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, Suzhou 215006, Chin)

机构地区：[1]苏州大学附属第一医院江苏省血液研究所卫生部血栓与止血重点实验室,215006 [2]苏州大学造血干细胞移植研究所,215213 [3]血液学协同创新中心江苏省干细胞与生物医用材料重点实验室省部共建国家重点实验室培养基地,215006

出　　处：《中华微生物学和免疫学杂志》2018年第2期98-105,共8页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金（81400145,81730003,81470346）;国家重点研发计划（2016YFC0902800,2017YFA0104502）;江苏高等院校优先学科发展规划（PAPD）;江苏省创新能力建设专项资助（BM2015004）;中国博士后科学基金项目（7131702415）;江苏省自然科学基金青年项目（BK201500352）

摘　　要：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.

关 键 词：生物指标 急性移植物抗宿主病 IL-27 无关供体移植 

分 类 号：R457.7[医药卫生—治疗学]