Department of Pediatrics, Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Transfusion. 2012 Feb;52(2):231-40. doi: 10.1111/j.1537-2995.2011.03255.x. Epub 2011 Jul 25.
Increased rates of red blood cell (RBC) alloimmunization in patients with sickle cell disease may be due to transfusion frequency, genetic predisposition, or immune dysregulation. To test the hypothesis that sickle cell pathophysiology influences RBC alloimmunization, we utilized two transgenic mouse models of sickle cell disease.
Transgenic sickle mice, which express human α and β(S) globin, were transfused with fresh or 14-day-stored RBCs containing the HOD (hen egg lysozyme, ovalbumin, and human Duffy(b) ) antigen; some recipients were inflamed with poly(I : C) before transfusion. Anti-HOD alloantibody responses were subsequently measured by enzyme-linked immunosorbent assay and flow crossmatch; a cohort of recipients had posttransfusion serum cytokines measured by bead array.
Both Berkeley and Townes homozygous (SS) and heterozygous (AS) mice had similar rates and magnitude of anti-HOD RBC alloimmunization after fresh HOD RBC transfusion compared with control animals; under no tested condition did homozygous SS recipients make higher levels of alloantibodies than control animals. Unexpectedly, homozygous SS recipients had blunted cytokine responses and lower levels of anti-HOD alloantibodies after transfusion of 14-day stored RBCs, compared with control animals.
In sum, homozygous β(S) expression and the ensuing disease state are not alone sufficient to enhance RBC alloimmunization to transfused HOD RBCs in two distinct humanized murine models of sickle cell disease under the conditions examined. These data suggest that other factors may contribute to the high rates of RBC alloimmunization observed in humans with sickle cell disease.
镰状细胞病患者的红细胞（RBC）同种免疫率增加可能是由于输血频率、遗传易感性或免疫失调。为了验证镰状细胞病理生理学影响 RBC 同种免疫的假设，我们利用了两种镰状细胞病的转基因小鼠模型。
表达人α和β(S)珠蛋白的转基因镰状细胞小鼠接受新鲜或 14 天储存的 RBC 输注，这些 RBC 含有 HOD（鸡卵溶菌酶、卵清蛋白和人 Duffy(b)）抗原；一些受者在输血前用聚（I:C）炎症。随后通过酶联免疫吸附试验和流式细胞交叉配型测量抗-HOD 同种抗体反应；一部分受者的输血后血清细胞因子通过 bead array 进行测量。
与对照动物相比，新鲜 HOD RBC 输注后，伯克利和汤斯纯合子（SS）和杂合子（AS）小鼠的抗-HOD RBC 同种免疫率和幅度相似；在任何测试条件下，纯合 SS 受者产生的同种抗体水平均未高于对照动物。出乎意料的是，与对照动物相比，纯合 SS 受者在输注 14 天储存的 RBC 后细胞因子反应减弱，抗-HOD 同种抗体水平较低。
总之，在两个不同的人源化镰状细胞病小鼠模型中，β(S)表达的纯合子和随之而来的疾病状态本身并不足以增强对输注 HOD RBC 的 RBC 同种免疫。这些数据表明，在镰状细胞病患者中观察到的高 RBC 同种免疫率可能还有其他因素。
