Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Transfusion. 2013 Jun;53(6):1319-27. doi: 10.1111/j.1537-2995.2012.03910.x. Epub 2012 Oct 3.
Alloimmunization to antigens on transfused red blood cells (RBCs) represents a major barrier to chronic transfusion. In extreme cases of multiple alloimmunization, clinicians may be faced with the decision of transfusing incompatible RBCs or risking death from lack of transfusion. The disastrous results of hemolytic transfusion reactions are well understood, and major pathways of clearance have been described. However, well described but poorly understood is the survival of a subset of incompatible donor RBCs during hemolysis, despite antibody binding.
We utilize a tractable murine model of incompatible transfusion in which RBCs from transgenic donor mice expressing human glycophorin A (hGPA) are transfused into recipients passively immunized with anti-hGPA.
As in humans, the majority of RBCs are cleared but a subset of incompatible donor RBCs persist in circulation, despite being bound by antibodies. Data contained herein reject the hypothesis that lack of clearance is due to insufficient antibody or overwhelming of phagocytic machinery; rather, we establish that surviving RBCs represent a distinct population resistant to clearance.
These studies demonstrate that surviving RBCs during incompatible transfusion can represent a population that is resistant to clearance.
针对输注的红细胞(RBC)上抗原的同种异体免疫是慢性输血的主要障碍。在多次同种异体免疫的极端情况下,临床医生可能面临输注不相容 RBC 的决定或因缺乏输血而死亡的风险。溶血输血反应的灾难性后果众所周知,并且已经描述了主要的清除途径。然而,尽管存在抗体结合,但仍有一部分不相容供体 RBC 在溶血期间存活,这是一个虽有描述但理解不足的问题。
我们利用一种可行的小鼠不相容输血模型,其中表达人糖蛋白 A(hGPA)的转基因供体小鼠的 RBC 被输注到被动免疫抗 hGPA 的受体中。
与人类一样,大多数 RBC 被清除,但尽管被抗体结合,仍有一部分不相容供体 RBC 持续存在于循环中。本文中的数据否定了清除不足是由于抗体不足或吞噬机制超负荷的假设;相反,我们确定存活的 RBC 代表了一种对清除具有抗性的独特群体。
这些研究表明,不相容输血期间存活的 RBC 可能代表一种对清除具有抗性的群体。