细胞因子组合辅助诊断眼部慢性移植物抗宿主病的临床研究  

Clinical study of the cytokine panel in the diagnosis of ocular chronic graft-versus-host disease

作　　者：程先静 吉锐 黄瑞昊 黄世勤 范围 赵元程 袁容娣 王筱淇 张曦 Cheng Xianjing;Ji Rui;Huan Ruihao;Huang Shiqin;Fan Wei;Zhao Yuancheng;Yuan Rongdi;Wang Xiaoqi;Zhang Xi(Medical Center of Hematology,Xinqiao Hospital of Army Medical University,Chongqing Key Laboratory of Hematology and Micoenvironment,State Key Laboatory of Trauma and Chemical Poisoning,Chongqing 400037,China;Department of Ophthalmology,Xinqiao Hospital,Army Medical University,Chongqing 400037,China;Jinfeng Laboratory,Chongqing 400037,China)

机构地区：[1]陆军军医大学第二附属医院血液病医学中心,全军临床重点专科,创伤与化学中毒国家重点实验室,重庆市医学重点学科,血液病与微环境重庆市重点实验室,重庆400037 [2]陆军军医大学新桥医院眼科,重庆400037 [3]金凤实验室,重庆400037

出　　处：《中华血液学杂志》2024年第3期242-248,共7页Chinese Journal of Hematology

基　　金：国家重点研发计划(2022YFA1103300、2022YFA1103304);国家血液系统疾病临床医学研究中心2020年度开放课题(2020ZKZC02);重庆市自然科学基金创新群体科学基金(cstc2021jcyj-cxttX0001);新桥医院青年博士人才孵化计划(2022YQB004)。

摘　　要：目的探索细胞因子与眼部慢性移植物抗宿主病(cGVHD)的相关性,筛选眼部cGVHD的特异性生物标志物。方法通过建立小鼠cGVHD模型,探讨cGVHD与血清细胞因子相关性。根据动物实验结果和文献检索,确定了16种细胞因子组合,使用酶联免疫吸附试验(ELISA)比较从2017年6月至2022年3月在陆军军医大学新桥医院血液病医学中心接受异基因造血干细胞移植后发生眼部cGVHD和未发生眼部cGVHD患者的血清与泪液细胞因子表达水平。结果①与对照组比较,cGVHD小鼠血清IL-1β、IL-6、IL-8、IL-17、IFN-γ、CX3CL1、CXCL11、CXCL13、CCL11、CCL19浓度升高(P<0.05);②患者血清和泪液细胞因子检测中,与未发生眼部cGVHD患者相比,眼部cGVHD患者血清细胞因子IL-8浓度升高(P=0.032,AUC=0.678)、IL-10浓度降低(P=0.030,AUC=0.701),泪液IL-8、IFN-γ、CXCL9和CCL17表达水平升高,而IL-10和CCL19表达水平较低(P<0.05,AUC值均>0.7),并且泪液细胞因子与眼部cGVHD疾病眼表参数相关。结论泪液细胞因子较血清细胞因子诊断眼部cGVHD更具有特异性与敏感性。泪液细胞因子IL-8、IL-10、IFN-γ、CXCL9、CCL17和CCL19可以作为移植后眼部cGVHD诊断性生物标志物,对其临床诊断具有一定价值。Objective To investigate the association between cytokines and ocular chronic graft-versus-host disease(cGVHD)and identify specific biomarkers for ocular cGVHD to enhance clinical diagnosis,treatment,and evaluation.Methods A mouse model of cGVHD was established to explore the correlation between cGVHD and serum cytokines.Based on the findings from the animal experiments and literature review,a panel of 16 cytokine combinations was identified.Enzyme-linked immunosorbent assay(ELISA)was used to compare the cytokine concentrations in the serum and tear samples from patients who underwent allogeneic hematopoietic stem cell transplantation from June 2017 to March 2022 at the Medical Center of Hematology,Xinqiao Hospital,Army Medical University.Results①Compared with the control group,mice with cGVHD exhibited elevated serum IL-1β,IL-6,IL-8,IL-17,IFN-γ,CX3CL1,CXCL11,CXCL13,CCL11,and CCL19 concentrations(all P<0.05).②Analysis of the cytokine profilesof the serum and tear samples revealed that compared with patients without ocular cGVHD,those with ocular cGVHD exhibited increased serum IL-8[P=0.032,area under the curve(AUC)=0.678];decreased serum IL-10(P=0.030,AUC=0.701);elevated IL-8,IFN-γ,CXCL9,and CCL17 in tear samples;and lower IL-10 and CCL19 in tear samples(all P<0.05,all AUC>0.7).Moreover,cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD.Conclusions Tear fluid demonstrates greater specificity and sensitivity as a biomarker for diagnosing ocular cGVHD than serum biomarkers.Among the identified cytokines in tear samples,IL-8,IL-10,IFN-γ,CXCL9,CCL17,and CCL19 serve as diagnostic biomarkers for ocular cGVHD post-transplantation,offering practical reference value for diagnosis.

关 键 词：异基因造血干细胞移植 眼部慢性移植物抗宿主病 泪液 细胞因子 生物标志物 

分 类 号：R73[医药卫生—肿瘤]