Cheng X J, Ji R, Huan R H, Huang S Q, Fan W, Zhao Y C, Yuan R D, Wang X Q, Zhang X
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.
Zhonghua Xue Ye Xue Za Zhi. 2024 Mar 14;45(3):242-248. doi: 10.3760/cma.j.cn121090-20231031-00242.
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. 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. 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 <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 [=0.032, area under the curve (AUC) =0.678]; decreased serum IL-10 (=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 <0.05, all AUC>0.7). Moreover, cytokines in tear samples showed correlations with ocular surface parameters related to ocular cGVHD. 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.
为研究细胞因子与眼部慢性移植物抗宿主病（cGVHD）之间的关联，并确定眼部cGVHD的特异性生物标志物，以加强临床诊断、治疗及评估。建立cGVHD小鼠模型，以探索cGVHD与血清细胞因子之间的相关性。基于动物实验结果及文献综述，确定了一组16种细胞因子组合。采用酶联免疫吸附测定（ELISA）比较2017年6月至2022年3月在陆军军医大学新桥医院血液科医疗中心接受异基因造血干细胞移植患者血清和泪液样本中的细胞因子浓度。①与对照组相比，cGVHD小鼠血清白细胞介素-1β（IL-1β）、IL-6、IL-8、IL-17、干扰素-γ（IFN-γ）、CX3CL1、CXCL11、CXCL13、CCL11和CCL19浓度升高（均<0.05）。②血清和泪液样本的细胞因子谱分析显示，与无眼部cGVHD的患者相比，眼部cGVHD患者血清IL-8升高[=0.032，曲线下面积（AUC）=0.678]；血清IL-10降低（=0.030，AUC=0.701）；泪液样本中IL-8、IFN-γ、CXCL9和CCL17升高；泪液样本中IL-10和CCL19降低（均<0.05，所有AUC>0.7）。此外，泪液样本中的细胞因子与眼部cGVHD相关的眼表参数存在相关性。作为眼部cGVHD的生物标志物，泪液比血清生物标志物具有更高特异性和敏感性。在泪液样本中鉴定出的细胞因子中，IL-8、IL-10、IFN-γ、CXCL9、CCL17和CCL19可作为移植后眼部cGVHD的诊断生物标志物，为诊断提供实用参考价值。
