Transfusion of minor histocompatibility antigen-mismatched platelets induces rejection of bone marrow transplants in mice
Transfusion of minor histocompatibility antigen-mismatched platelets induces rejection of bone marrow transplants in mice
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DOI：
10.1172/jci39590
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发表时间：
2009-09-01
影响因子：
15.9
通讯作者：
Zimring, James C.
中科院分区：
文献类型：
--
作者：
Patel, Seema R.;Cadwell, Chantel M.;Zimring, James C.
骨髓移植（BMT）是一种治疗非恶性血液病的方法。然而，与进行BMT治疗恶性血液病时使用的严格预处理方案相比，在非恶性血液病的背景下使用的强度降低的预处理方案导致BMT排斥反应的发生率显著更高，这可能是由于免疫系统完整所致。相关患者群体通常接受输血支持，通常包括血小板，BMT排斥反应的频率与输血频率相关。在这里，我们证明了对输注血小板的免疫力有助于小鼠随后的BMT排斥反应，即使BMT供体和受体是MHC匹配的。我们使用MHC匹配的骨髓，因为尽管对输注血小板的免疫性最好表征为与HLA特异性抗体相关，但此类抗体不太可能在HLA匹配的临床BMT排斥中发挥作用。然而，骨髓是不匹配的，在临床上的次要组织相容性抗原，如血小板携带的，我们报告说，输血的次要组织相容性抗原不匹配的血小板诱导随后的骨髓移植排斥反应。这些研究结果表明，以前不受重视的后遗症的免疫血小板移植的背景下，并建议的策略，以占轻微的组织相容性错配可能有助于减少人类患者的骨髓移植排斥反应的机会。
Bone marrow transplantation (BMT) represents a cure for nonmalignant hematological disorders. However, compared with the stringent conditioning regimens used when performing BMT to treat hematological malignancies, the reduced intensity conditioning regimen used in the context of nonmalignant hematological disorders leads to substantially higher rates of BMT rejection, presumably due to an intact immune system. The relevant patient population typically receives transfusion support, often including platelets, and the frequency of BMT rejection correlates with the frequency of transfusion. Here, we demonstrate that immunity to transfused platelets contributes to subsequent BMT rejection in mice, even when the BMT donor and recipient are MHC matched. We used MHC-matched bone marrow because, although immunity to transfused platelets is best characterized in relation to HLA-specific antibodies, such antibodies are unlikely to play a role in clinical BMT rejection that is HLA matched. However, bone marrow is not matched in the clinic for minor histocompatibility antigens, such as those carried by platelets, and we report that transfusion of minor histocompatibility antigen-mismatched platelets induced subsequent BMT rejection. These findings indicate previously unappreciated sequelae of immunity to platelets in the context of transplantation and suggest that strategies to account for minor histocompatibility mismatching may help to reduce the chance of BMT rejection in human patients.