血浆Reg3α蛋白水平与肠道aGVHD的相关性研究  

Correlation of The Level of Reg3α Protein in Plasma with Gastrointestinal Acute Graft-Versus-Host Disease

作　　者：蔡成森[1] 陈广华[1] 孙爱宁[1] 乔曼[1] 刘慧文[1] 陈峰[1] 王荧[1] 仇惠英[1] 韩悦[1] 马骁[1] 唐晓文[1] 金正明[1] 傅琤琤[1] 吴德沛[1] 

机构地区：[1]苏州大学附属第一医院血液科,江苏苏州215006

出　　处：《中国实验血液学杂志》2014年第3期785-790,共6页Journal of Experimental Hematology

基　　金：江苏高校优势学科建设工程资助项目(2010);江苏省临床医学中心项目(ZX201102);国家自然科学基金项目(81270617);高校博士点基金项目(20113201110010)

摘　　要：本研究探讨血浆Reg3α蛋白水平与异基因造血干细胞移植(allo-HSCT)后肠道急性移植物抗宿主病(GIaGVHD)的临床诊断及预后的相关性。以我院2011年12月至2012年12月行allo-HSCT的103例患者为研究对象。采集移植前9 d、0 d、移植后14 d、移植后28 d、腹泻时多个时间点抗凝外周血,对发生aGVHD的患者进一步采集治疗1周及4周后抗凝外周血,采用ELISA方法检测血浆Reg3α蛋白浓度。结果表明,103例患者中无aGVHD17例,非aGVHD腹泻27例,单纯皮肤aGVHD 10例,Ⅰ-Ⅱ度肠道aGVHD(GI-aGVHD)17例,Ⅲ-Ⅳ度GI-aGVHD32例。GI-aGVHD患者和非aGVHD腹泻患者腹泻时血浆Reg3α蛋白水平分别为111.5(54.7-180.2)ng/ml和23.9(14.5-89.5)ng/ml(P<0.001)。Ⅲ-Ⅳ度GI-aGVHD患者治疗4周后,治疗有效组17例与治疗无效组7例血浆Reg3α蛋白水平分别为137.2(51.7-205.4)ng/ml和679.4(122.3-896.8)ng/ml(P=0.028)。治疗无效组7例全部死于aGVHD相关的多器官功能衰竭。血浆Reg3α蛋白浓度≥87.73 ng/ml时预测Ⅲ-Ⅳ度GI-aGVHD的鉴别效度即曲线下面积最大(AUC=0.902),其诊断Ⅲ-Ⅳ度GI-aGVHD敏感度为81.48%,特异性为82.86%。移植后Reg3α蛋白高水平组(≥87.73 ng/ml)患者Ⅲ-Ⅳ度GI-aGVHD发生率明显高于低水平组(<87.73 ng/ml)(P<0.001)。结论:移植后血浆Reg3α蛋白水平升高提示Ⅲ-Ⅳ度GI-aGVHD的发生,Ⅲ-Ⅳ度GI-aGVHD患者免疫抑制治疗后血浆Reg3α蛋白水平不降低与预后不良相关,血浆Reg3α蛋白水平可作为提示GI-aGVHD的生物学标志物。This study was purposed to explore the correlation of regenerating Islet-derived 3-alpha（Reg3α） protein level in plasma with the diagnosis and prognosis of the gastrointestinal acute graft-versus-host disease （GI-aGVHD） after all-HSCT, 103 patients who underwent allogeneic hematopoietic stem cell transplantation （allo-HSCT） were observed in our hospital from December 2011 to December 2012. Peripheral blood samples were routinely collected at 9 d before allo-HSCT, 0 d, 14 d, 28 d after allo-HSCT as well as in aGVHD and at the 1 and 4 weeks after aGVHD therapy. The plasma concentrations of Reg3et were measured by using ELISA kit. The results indicated that among the 103 patients, 17 cases never developed aGVHD symptoms （no-aGVHD）, 27 cases presented with non-aGVHD associated diarrhea, 10 cases presented with isolated skin aGVHD, 17 cases developed grades Ⅰ-Ⅱ GI-aGVHD, 32 cases with grades Ⅲ-Ⅳ GI-aGVHD. The plasma concentrations of Reg3α in group of patients with GI-aGVHD and group of non-aGVHD diarrhea were 111.5 （54.7 - 180.2） and 23.9 （ 14.5 - 89.5 ） ng/ml respectively with significant difference（ P 〈 0. 001 ）. The plasma concentrations of Reg3α in 17 patients of grades Ⅲ-Ⅳ GI-aGVHD who experienced a completeor partial response and 7 patients who had no response to therapy at 4 weeks were 137.2（51.7 - 205.4） and 679.4 （ 122.3 - 896.8 ） ng/ml respectively with the significant difference （ P = 0. 028 ）. All of the patients who had no response to therapy died of aGVHD associated multiple organ failure. The area under the ROC curve was 0. 902 when plasma concentration of Reg3α was set at 87.73 ng/ml. The sensitivity was 81.48% and the specificity was 82.86% when the critical value was used in diagnosis of grades Ⅲ-Ⅳ GI-aGVHD. The probability of grades Ⅲ-Ⅳ GI-aGVHD had statistical difference above and below 87.73 ng/ml after allo-HSCT（ P 〈 0.001 ）. It is concluded that the increate of plasma Reg3α level after transplantation suggests the incidinc

关 键 词：异基因造血干细胞移植 急性移植物抗宿主病 Reg3α蛋白 血浆 

分 类 号：R457.7[医药卫生—治疗学]