Arthur Connie M, Allen Jerry William L, Verkerke Hans, Yoo Justin, Jajosky Ryan P, Girard-Pierce Kathryn, Chonat Satheesh, Zerra Patricia, Maier Cheryl, Rha Jen, Fasano Ross, Josephson Cassandra D, Roback John D, Stowell Sean R
Center for Transfusion Medicine and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
Joint Program in Transfusion Medicine, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and.
Blood Adv. 2021 Jan 26;5(2):527-538. doi: 10.1182/bloodadvances.2020002695.
Incompatible red blood cell (RBC) transfusion can result in life-threatening transfusion complications that can be challenging to manage in patients with transfusion-dependent anemia. However, not all incompatible RBC transfusions result in significant RBC removal. One factor that may regulate the outcome of incompatible RBC transfusion is the density of the incompatible antigen. Despite the potential influence of target antigen levels during incompatible RBC transfusion, a model system capable of defining the role of antigen density in this process has not been developed. In this study, we describe a novel model system of incompatible transfusion using donor mice that express different levels of the KEL antigen and recipients with varying anti-KEL antibody concentrations. Transfusion of KEL+ RBCs that express high or moderate KEL antigen levels results in rapid antibody-mediated RBC clearance. In contrast, relatively little RBC clearance was observed following the transfusion of KEL RBCs that express low KEL antigen levels. Intriguingly, unlike RBC clearance, loss of the KEL antigen from the transfused RBCs occurred at a similar rate regardless of the KEL antigen density following an incompatible transfusion. In addition to antigen density, anti-KEL antibody levels also regulated RBC removal and KEL antigen loss, suggesting that antigen density and antibody levels dictate incompatible RBC transfusion outcomes. These results demonstrate that antibody-induced antigen loss and RBC clearance can occur at distinct antigen density thresholds, providing important insight into factors that may dictate the outcome of an incompatible RBC transfusion.
不相容的红细胞（RBC）输血可导致危及生命的输血并发症，这对于依赖输血的贫血患者来说可能难以处理。然而，并非所有不相容的RBC输血都会导致大量RBC清除。一个可能调节不相容RBC输血结果的因素是不相容抗原的密度。尽管在不相容RBC输血过程中靶抗原水平有潜在影响，但尚未开发出一种能够确定抗原密度在此过程中作用的模型系统。在本研究中，我们描述了一种新型的不相容输血模型系统，使用表达不同水平KEL抗原的供体小鼠和具有不同抗KEL抗体浓度的受体。输注表达高或中等KEL抗原水平的KEL+RBC会导致抗体介导的RBC快速清除。相比之下，输注表达低KEL抗原水平的KEL RBC后，观察到的RBC清除相对较少。有趣的是，与RBC清除不同，无论不相容输血后KEL抗原密度如何，输注的RBC中KEL抗原的丢失速率相似。除了抗原密度外，抗KEL抗体水平也调节RBC清除和KEL抗原丢失，这表明抗原密度和抗体水平决定了不相容RBC输血的结果。这些结果表明，抗体诱导的抗原丢失和RBC清除可以在不同的抗原密度阈值下发生，这为可能决定不相容RBC输血结果的因素提供了重要的见解。
