血友病A是基因突变致凝血因子VIII活性缺乏的遗传性出血性疾病，凝血因子替代治疗可控制出血，但抑制物产生使之失效。抑制物产生目前是血友病A治疗最大阻碍，机制未明；已知Th17/Treg失衡在免疫失耐受中发挥重要作用，近年虽有小鼠实验证实Treg细胞与血友病抑制物产生相关，但抑制物产生是否与Th17/Treg轴失衡有关尚不清。推测，Th17/Treg轴失衡与血友病抑制物产生相关，调整其平衡可防控抑制物。本课题拟对儿童重型血友病A开展连续、规律的抑制物及Th17、Treg监测，动态观察在接触外源性因子后患儿抑制物和Th17、Treg水平变化，应用FVIII-/-鼠体内实验尝试调整Th17/Treg轴平衡预防抑制物产生。应用上述方法来证实Th17/Treg失衡在血友病A抑制物产生中作用，探索调整Th17/Treg轴平衡来防控抑制物，为阐明血友病抑制物发生机制及提出有效防控策略提供理论依据和思路。

Hemophilia A is one inherited bleeding disease with factor VIII deficiency caused by gene mutation，the concentrates replacement is the only effective method to control bleeding, but the inhibitor ineffects it. The inhibitor development is the biggest obstacle in hemophilia A care in the world, the mechnism is not very clear. The imbanlance of Th17/Treg axis plays key role on immune tolerance, and currently,although the relationship between inhibitor development and Regulatory T cell (Treg cell) in mice model has been proved, Th17/Treg axis imbalance hasn't been proved in the inhibitor developmente in hemophilia. We speculate that, there would exist the relationship between the imbalance of Th17/Treg axis and inhibitor development in hemophilia A patients, maintain its balance might prevent the inhibitor development. Our study is to investigate on severe hemophilia A children, to recode the clinical data, monitor the levels of inhibitor and Th17,Treg cells periodically and continuously, to observe the inhibitor development and affect on Th17/Treg axis during the course of hemophilia A children from unexposure to exposure to exogenous VIII factor, try to regulate and maintain Th17/Treg axis balance in FVIII-/- mice to prevent the inhibitor development. Aim is to establish basic and provide the new method for the inhibitor development and provention machanism in hemophilia management.