BloodworksNW Research Institute.
Department of Laboratory Medicine, School of Medicine, University of Washington, Seattle, Washington, USA.
Curr Opin Hematol. 2018 Nov;25(6):473-481. doi: 10.1097/MOH.0000000000000459.
Pathogenic autoantibodies directed against red blood cells (RBCs) may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Much of what is known about the etiology and pathogenesis of AIHA has been learned from observations made in human patients and murine models, but many questions remain; importantly, it is still unclear why some people generate RBC-specific autoantibodies. The combination of technological advancements applied to existing models and the development of new AIHA murine models will continue to provide considerable insight into the initiation of AIHA and provide a platform for the design of more effective therapies.
Advancements in well described murine models of AIHA show that reticulocytes are preferentially targeted by anti-RBC autoantibodies and an increase in oxidative stress may trigger autoantibody production. Additionally, a new murine model of erythrocyte autoreactivity demonstrates that T cell tolerance is the stopgap for autoimmunity. Moreover, unlike many self-antigens, data suggest that RBC self-antigens are not presented in the thymus thereby escaping the scrutiny of T cell central tolerance mechanisms and placing emphasis on peripheral tolerance instead. Information gained from this new model provide novel insight into how the immune system responds to RBC autoantigens and provides a tractable platform to discover new therapies for AIHA.
Murine models of AIHA have provided significant understanding into the risk factors for AIHA. The application of new technologies and models of erythrocyte autoreactivity is a pathway with the potential to elucidate how tolerance to RBC autoantigens is established, maintained, and broken down.
针对红细胞（RBC）的致病性自身抗体可能导致自身免疫性溶血性贫血（AIHA），这是一种严重且有时致命的疾病。我们对 AIHA 的病因和发病机制的了解主要来自于对人类患者和小鼠模型的观察，但仍有许多问题尚未解决；重要的是，目前仍不清楚为什么有些人会产生针对 RBC 的自身抗体。将应用于现有模型的技术进步与新的 AIHA 小鼠模型相结合，将继续为 AIHA 的启动提供重要的见解，并为设计更有效的治疗方法提供平台。
在 AIHA 的描述良好的小鼠模型中取得的进展表明，网织红细胞是抗 RBC 自身抗体的优先靶标，氧化应激的增加可能触发自身抗体的产生。此外，一种新的红细胞自身反应性小鼠模型表明，T 细胞耐受是自身免疫的权宜之计。此外，与许多自身抗原不同，数据表明 RBC 自身抗原不在胸腺中表达，从而逃避了 T 细胞中枢耐受机制的审查，并强调了外周耐受。从这个新模型中获得的信息为免疫系统如何对 RBC 自身抗原作出反应提供了新的见解，并为 AIHA 的新疗法提供了一个可行的平台。
AIHA 的小鼠模型为 AIHA 的危险因素提供了重要的认识。应用新技术和红细胞自身反应性模型是阐明如何建立、维持和打破对 RBC 自身抗原的耐受的潜在途径。
