Department Pediatrics, Indiana University, Indianapolis, Indiana, USA.
Curr Opin Hematol. 2018 Sep;25(5):365-372. doi: 10.1097/MOH.0000000000000446.
Hemophilia is an X-linked blood coagulation genetic disorder, which can cause significant disability. Replacement therapy for coagulation factor VIII (hemophilia A) or factor IX (hemophilia B) may result in the development of high-affinity alloantibodies ('inhibitors') to the replacement therapy, thus making it ineffective. Therefore, there is interest in directing immunological responses towards tolerance to infused factors.
In this review, we will discuss latest advancements in the development of potentially less immunogenic replacement clotting factors, optimization of current tolerance induction protocols (ITI), preclinical and clinical data of pharmacological immune modulation, hepatic gene therapy, and the rapidly advancing field of cell therapies. We will also evaluate publications reporting data from preclinical studies on oral tolerance induction using chloroplast-transgenic (transplastomic) plants.
Until now, no clinical prophylactic immune modulatory protocol exists to prevent inhibitor formation to infused clotting factors. Recent innovative technologies provide hope for improved eradication and perhaps even prevention of inhibitors.
血友病是一种 X 连锁的血液凝血遗传疾病，可导致严重残疾。凝血因子 VIII（血友病 A）或因子 IX（血友病 B）的替代疗法可能会导致对替代疗法产生高亲和力的同种异体抗体（“抑制剂”），从而使其无效。因此，人们有兴趣将免疫反应引导至对输注因子的耐受。
在这篇综述中，我们将讨论开发潜在免疫原性更低的替代凝血因子的最新进展、当前诱导耐受方案（ITI）的优化、药物免疫调节的临床前和临床数据、肝基因治疗以及细胞治疗领域的快速发展。我们还将评估报告使用叶绿体转基因（转质体）植物进行口服耐受诱导的临床前研究数据的出版物。
到目前为止，还没有临床预防性免疫调节方案可用于预防输注凝血因子引起的抑制剂形成。最近的创新技术为改善清除甚至可能预防抑制剂提供了希望。
