不同血友病A患者临床表型中CD4^(+)CD25^(+)调节T细胞差异及其与FⅧ抑制物阳性的关系  

The difference of CD4^(+)CD25^(+)regulatory T cells in different clinical phenotypes of hemophilia A and its relationship with positive FⅧinhibitor

作　　者：于冬雯[1] 郑炜[1] 刘登辉 杨瑛[1] YU Dongwen;ZHENG Wei;LIU Denghui;YANG Ying(Department of Hematology,Dalian Central Hospital,Dalian 116089,Shandong,China)

机构地区：[1]大连市中心医院血液科,辽宁大连116089

出　　处：《西部医学》2025年第4期564-569,共6页Medical Journal of West China

基　　金：大连市医学科学研究计划项目(1911006)。

摘　　要：目的探究不同血友病A(HA)患者临床表型中CD4^(+)CD25^(+)调节T细胞差异及其与凝血因子Ⅷ(FⅧ)抑制物阳性的关系。方法选择2020年2月—2023年2月在我院接受治疗的HA患者105例作为观察对象,以自发性出血频率6次/年为分界点,年出血频率≤6次/年为临床表现轻度表型组(简称轻度组,n=42),>6次/年为临床表现重度表型组(简称重度组,n=63),比较两组患者临床资料。根据FⅧ抑制物检测结果,将HA患者分为阳性组(n=16)和非阳性组(n=89),通过单因素和多因素Logistic分析FⅧ抑制物阳性的影响因素。应用样条函数与Logistic回归相结合的限制性立方样条法分析CD4^(+)CD25^(+)T细胞与FⅧ抑制物阳性的剂量-反应关系。结果轻度组和重度组在血小板计数(PLT)、FⅧ:C、CD4^(+)T细胞、CD4^(+)T细胞/CD8^(+)T细胞、CD4^(+)CD25^(+)T细胞比较差异统计学意义(P<0.05)。单因素和多因素Logistic回归分析结果显示,年龄、HA严重程度、基因突变类型、首次暴露原因、累积暴露日是HA患者FⅧ抑制物阳性的危险因素(P<0.05),CD4^(+)CD25^(+)T细胞水平是HA患者FⅧ抑制物阳性的保护因素(P<0.05)。CD4^(+)CD25^(+)T细胞与FⅧ抑制物阳性关系的Logistic回归分析,调整混杂因素后,CD4^(+)CD25^(+)T细胞水平3.9%~4.4%、<3.9%与FⅧ抑制物阳性显著相关。限制性立方样条分析结果显示,无论轻度组或重度组,CD4^(+)CD25^(+)T细胞水平的连续变化与FⅧ抑制物阳性的关联强度都呈非线性剂量-反应关系(非线性检测,P<0.001)。结论不同临床表型的HA患者的CD4^(+)CD25^(+)T细胞水平具有显著差异,CD4^(+)CD25^(+)T细胞水平随着HA严重程度增加而降低;调整混杂因素后,CD4^(+)CD25^(+)T细胞水平与HA患者FⅧ抑制物阳性仍显著相关。Objective To explore the difference of CD4^(+)CD25^(+)regulatory T cells in different clinical phenotypes of hemophilia A(HA)and its relationship with positive factorⅧ(FⅧ)inhibitors.Methods A total of 105 HA patients who received treatment in our hospital from February 2020 to February 2023 were selected as the research objects,with the frequency of spontaneous bleeding 6 times/year as the dividing point,the annual bleeding frequency≤6 times/year was considered as the clinical manifestations of mild group(n=42),and the annual bleeding frequency>6 times/year was considered as the clinical manifestations of severe group(n=63),and the clinical data of the two groups were compared.According to the results of FⅧinhibitor test,HA patients were divided into positive group(n=16)and non-positive group(n=89),and the influencing factors of FⅧinhibitor positive were analyzed by univariate and multivariate Logistic analysis.The dose-response relationship between CD4^(+)CD25^(+)T cells and positive FⅧinhibitor was analyzed by restricted cubic spline method combined with Logistic regression.Results There were statistical differences among Platelet count(PLT),FⅧ:C,CD4^(+)T cells,CD4^(+)T cells/CD8^(+)T cells,and CD4^(+)CD25^(+)T cells between the mild and severe groups(P<0.05).Univariate and multivariate Logistic regression analysis showed that age,HA severity,fund mutation type,cause of first exposure,and cumulative exposure day were risk factors for FⅧinhibitor positive in HA patients(P<0.05),and CD4^(+)CD25^(+)T cell level was protective factor for FⅧinhibitor positive in HA patients(P<0.05).Logistic regression analysis of the positive relationship between CD4^(+)CD25^(+)T cells and FⅧinhibitor were showed,after adjusting confounding factors,CD4^(+)CD25^(+)T cell levels of 3.9~4.4%,<3.9%were significantly correlated with positive FⅧinhibitor.The results of restricted cubic spline analysis showed a nonlinear dose-response relationship between continuous changes in CD4^(+)CD25^(+)T cell levels and positive

关 键 词：血友病A 临床表型 调节性T细胞 抑制物 限制性立方样条 

分 类 号：R554.1[医药卫生—血液循环系统疾病]