Alloimmunization to transfused HOD red blood cells is not increased in mice with sickle cell disease.
Alloimmunization to transfused HOD red blood cells is not increased in mice with sickle cell disease.
复制标题
在患有镰状细胞病的小鼠中，输注的 HOD 红细胞的同种免疫并未增加。
DOI：
10.1111/j.1537-2995.2011.03255.x
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发表时间：
2012
期刊：
影响因子：
2.9
通讯作者：
Zimring,JamesC
中科院分区：
文献类型：
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作者：
Hendrickson,JeanneE;Hod,EldadA;Perry,JenniferR;Ghosh,Samit;Chappa,Prasanthi;Adisa,Olufolake;Kean,LeslieS;Ofori-Acquah,SolomonF;Archer,DavidR;Spitalnik,StevenL;Zimring,JamesC
背景：镰状细胞病患者红细胞同种异体免疫率的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，我们利用了两种转基因小鼠模型的镰状细胞diseases.Study设计和方法：转基因镰状细胞小鼠，表达人类α和β球蛋白，输注新鲜或14天储存的红细胞含有HOD（鸡蛋溶菌酶，卵清蛋白，和人Duffyb）抗原;一些收件人在输血前与聚（I：C）发炎。 随后通过酶联免疫吸附试验和流式交叉配血测定抗HOD同种抗体反应;一组受者的输血后血清细胞因子通过微珠阵列测定。结果：伯克利和汤斯纯合子（SS）和杂合子（AS）小鼠与对照动物相比，新鲜HOD RBC输注后抗HOD RBC同种免疫的速率和幅度相似;在任何测试条件下，纯合子SS受者的同种抗体水平均高于对照动物。出乎意料的是，纯合子SS受体有钝化细胞因子反应和较低水平的抗HOD同种抗体输血后14天存储的红细胞，与control animals.Conclusions相比：总之，纯合子β S表达和随后的疾病状态是不足以单独增强红细胞同种免疫输血HOD红细胞在两个不同的人源化小鼠模型的镰状细胞病的条件下检查。这些数据表明，其他因素可能有助于在镰状细胞病患者中观察到的RBC同种异体免疫的高比率。
BACKGROUND: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.STUDY DESIGN AND METHODS:Transgenic sickle mice, which express human α and βSglobin, were transfused with fresh or 14‐day‐stored RBCs containing the HOD (hen egg lysozyme, ovalbumin, and human Duffyb) 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.RESULTS: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.CONCLUSIONS:In sum, homozygous βSexpression 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.