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.
Abstract
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.Results ① Compared 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).(2)Analysis of the cytokine profiles of 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.
基金项目
国家重点研发计划(2022YFA1103300)
国家重点研发计划(2022YFA1103304)
国家血液系统疾病临床医学研究中心开放课题(2020)(2020ZKZC02)
重庆市自然科学基金创新群体项目(cstc2021jcyjcxttX0001)
新桥医院青年博士人才孵化计划(2022YQB004)
NETL
NSTL
维普
万方数据