血友病因子VIII治疗。免疫耐受。临床视角。

Hemophilia factor VIII therapy. Immunological tolerance. A clinical perspective.

作者信息

White G C, Greenwood R, Escobar M, Frelinger J A

机构信息

Center for Thrombosis and Hemostasis, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill 27599-7035, USA.

出版信息

Haematologica. 2000 Oct;85(10 Suppl):113-6.

PMID:11187862

Abstract

Human alloantibodies to factor VIII occur in 15-50% of patients with severe hemophilia A. The development of these inhibitory alloantibodies prevents treatment with replacement factor VIII and places the patient at higher risk for complications from bleeding. Immune tolerance to factor VIII can be achieved in patients with inhibitors through the regular administration of factor VIII. The mechanism by which immune tolerance is achieved is unclear but the regular administration of factor VIII is believed to interrupt the normal immune mechanisms, perhaps by altering antigen presentation and inducing T or B cell anergy. The development of immune tolerance in hemophilia can be seen as a potential model for the development of methods for inducing tolerance to other alloimmune and autoimmune disorders.

摘要

15%至50%的重度甲型血友病患者体内会产生针对凝血因子VIII的人同种抗体。这些抑制性同种抗体的产生会妨碍用凝血因子VIII替代疗法进行治疗，并使患者面临更高的出血并发症风险。对于体内有抑制物的患者，通过定期注射凝血因子VIII可实现对凝血因子VIII的免疫耐受。实现免疫耐受的机制尚不清楚，但人们认为定期注射凝血因子VIII可能会干扰正常免疫机制，或许是通过改变抗原呈递并诱导T细胞或B细胞无反应性来实现的。血友病中免疫耐受的发展可被视为开发诱导对其他同种免疫和自身免疫性疾病产生耐受方法的潜在模型。