Division of Pediatric Hematology/Oncology, AFLAC Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Transfusion. 2010 Mar;50(3):642-8. doi: 10.1111/j.1537-2995.2009.02481.x. Epub 2009 Nov 9.
Red blood cell (RBC) alloimmunization can be a serious complication of blood transfusion, but factors influencing the development of alloantibodies are only partially understood. Within FDA-approved time limits, RBCs are generally transfused without regard to length of storage. However, recent studies have raised concerns that RBCs stored for more than 14 days have altered biologic properties that may affect medical outcomes. To test the hypothesis that storage time alters RBC immunogenicity, we utilized a murine model of RBC storage and alloimmunization.
Blood from transgenic HOD donor mice, which express a model antigen (hen egg lysozyme [HEL]) specifically on RBCs, was filter leukoreduced and stored for 14 days under conditions similar to those used for human RBCs. Fresh or 14-day-stored RBCs were transfused into wild-type recipients. The stability of the HOD antigen and posttransfusion RBC survival were analyzed by flow cytometry. RBC alloimmunization was monitored by measuring circulating anti-HEL immunoglobulin levels.
Transfusion of 14-day-stored, leukoreduced HOD RBCs resulted in 10- to 100-fold higher levels of anti-HEL alloantibodies as detected by enzyme-linked immunosorbent assay than transfusion of freshly collected, leukoreduced RBCs. RBC expression of the HOD antigen was stable during storage.
These findings demonstrate that HOD murine RBCs become more immunogenic with storage and generate the rationale for clinical trials to test if the same phenomenon is observed in humans. Length of storage of RBCs may represent a previously unappreciated variable in whether or not a transfusion recipient becomes alloimmunized.
红细胞（RBC）同种免疫可成为输血的严重并发症，但影响同种抗体产生的因素仅部分了解。在 FDA 批准的时间限制内，通常不考虑红细胞的储存时间而进行输血。然而，最近的研究引起了人们的关注，即储存超过 14 天的 RBC 具有改变的生物学特性，可能会影响医疗结果。为了检验储存时间改变 RBC 免疫原性的假设，我们利用了 RBC 储存和同种免疫的小鼠模型。
来自转基因 HOD 供体小鼠的血液，其在 RBC 上特异性表达一种模型抗原（鸡卵溶菌酶[HEL]），经过过滤去白细胞处理并在类似于人类 RBC 储存的条件下储存 14 天。新鲜或储存 14 天的 RBC 输注到野生型受体中。通过流式细胞术分析 HOD 抗原的稳定性和输血后 RBC 的存活率。通过测量循环抗 HEL 免疫球蛋白水平监测 RBC 同种免疫。
与输注新鲜采集的去白细胞 RBC 相比，输注储存 14 天的去白细胞 HOD RBC 导致抗 HEL 同种抗体的水平增加了 10 到 100 倍，通过酶联免疫吸附试验检测。在储存过程中，RBC 表达 HOD 抗原是稳定的。
这些发现表明，HOD 小鼠 RBC 在储存过程中变得更具免疫原性，并为临床试验提供了依据，以测试是否在人类中观察到相同的现象。RBC 的储存时间可能是输血受体是否发生同种免疫的一个以前未被认识到的变量。
