Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta/Emory University School of Medicine, Atlanta, GA, USA.
Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Transfus Med Rev. 2023 Jan;37(1):21-26. doi: 10.1016/j.tmrv.2022.12.009. Epub 2022 Dec 23.
RBC alloimmunization remains a significant barrier to ongoing transfusion therapy leading to morbidity, and in extreme cases mortality, due to delayed or insufficient units of compatible RBCs. In addition, the monitoring and characterization of alloantibodies, often with multiple specificities in a single patient, consumes substantial health care resources. Extended phenotypic matching has mitigated, but not eliminated, RBC alloimmunization and is only logistically available for specialized populations. Thus, RBC alloimmunization remains a substantial problem. In recent decades it has become clear that mechanisms of RBC alloimmunization are distinct from other antigens and lack of mechanistic understanding likely contributes to the fact that there are no approved interventions to prevent RBC alloimmunization from transfusion. The combination of human studies and murine modeling have identified several key factors in RBC alloimmunization. In both humans and mice, immunogenicity is a function of alloantigen copy number on RBCs. Murine studies have further shown that copy number not only changes rates of immunization but the mechanisms of antibody formation. This review summarizes the current understanding of quantitative and qualitative effects of alloantigen copy number on RBC alloimmunization.
红细胞同种异体免疫仍然是持续输血治疗的一个重大障碍，导致发病率，在极端情况下导致死亡率，原因是延迟或不足的相容红细胞单位。此外，同种抗体的监测和特征，通常在单个患者中具有多种特异性，消耗大量的医疗保健资源。扩展表型匹配减轻了，但没有消除红细胞同种异体免疫，并且仅对专门人群在后勤上可用。因此，红细胞同种异体免疫仍然是一个重大问题。近几十年来，人们已经清楚地认识到红细胞同种异体免疫的机制与其他抗原不同，并且缺乏对机制的理解可能是没有批准的干预措施来预防输血引起的红细胞同种异体免疫的原因。人类研究和小鼠模型的结合已经确定了红细胞同种异体免疫的几个关键因素。在人类和小鼠中，免疫原性是 RBC 上同种异体抗原数量的函数。小鼠研究进一步表明，拷贝数不仅改变了免疫的速度，而且改变了抗体形成的机制。这篇综述总结了目前对同种异体抗原拷贝数对 RBC 同种异体免疫的定量和定性影响的理解。
