Transfusion-induced alloimmunization and platelet refractoriness in a mouse model: mechanisms and interventions
Transfusion-induced alloimmunization and platelet refractoriness in a mouse model: mechanisms and interventions
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DOI：
10.1111/trf.13270
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发表时间：
2016-01-01
期刊：
影响因子：
2.9
通讯作者：
Zimring, James C.
中科院分区：
文献类型：
--
作者：
Waterman, Hayley R.;Kapp, Linda M.;Zimring, James C.
血小板（PLT）输注是血小板减少症患者维持止血的基本疗法。然而，一些患者变得对PLT上的抗原（通常为HLA）同种免疫，这可以由于抗体介导的清除而阻止PLT输血的功效。在极端情况下，患者与allimmunization多个HLA可以成为难治性PLT输血，这样，不充分的兼容PLT单位可以发现，以满足transmission needs.MATERIALS和METHODSAN在体内小鼠模型的PLT诱导allimmunization进行了改进，以包括输血与同种异体leukoreduced PLT和输血后PLT回收率的研究，允许评估allimmunization和难治性。使用缺失C3补体基因或Fc受体共同γ链的受体研究了抗体介导的PLT清除的基本机制。此外，通过在PLT输血前测试CTLA 4-IG施用来评估使用共刺激阻断作为治疗干预的功效。此外，抗-MHC的水平可预测给定动物的难治性程度。最后，共刺激阻断作为一种治疗方式，防止输血诱导的PLT refractorys. CONCLUSIONTOGether这些研究结果介绍了新的实验方法，基本机制的理解，和一个潜在的治疗干预同种异体免疫的MHC为基础的抗原输血血小板。
BACKGROUNDPlatelet (PLT) transfusions can be an essential therapy for patients with thrombocytopenia to maintain hemostasis. However, some patients become alloimmunized to antigens on PLTs (typically HLA), which can prevent efficacy of PLT transfusion due to antibody-mediated clearance. In extreme cases, patients with alloimmunization to multiple HLAs can become refractory to PLT transfusion, such that insufficient compatible PLT units can be found to meet transfusion needs.MATERIALS AND METHODSAn in vivo murine model of PLT-induced alloimmunization was refined so as to include both transfusion with allogeneic leukoreduced PLTs and studies of posttransfusion PLT recoveries, allowing assessment of alloimmunization and refractoriness. Basic mechanisms of antibody-mediated PLT clearance were investigated using recipients missing either the C3 complement gene or the common gamma chain for Fc receptors. In addition, the efficacy of using costimulatory blockade as a therapeutic intervention was assessed by testing CTLA4-Ig administration before PLT transfusion.RESULTSFc receptors (but not complement C3) are required for alloantibody-mediated PLT refractoriness. In addition, levels of anti-MHC predict the extent of refractoriness in a given animal. Finally, costimulatory blockade as a therapeutic modality prevents transfusion-induced PLT refractoriness.CONCLUSIONSTogether these findings introduce new experimental methods, basic mechanistic understanding, and a potential therapeutic intervention for alloimmunization to MHC-based antigens on transfused PLTs.