In utero exposure to alloantigens primes alloimmunization to platelet transfusion in mice.
In utero exposure to alloantigens primes alloimmunization to platelet transfusion in mice.
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在子宫内暴露于异体抗原引发小鼠血小板输注的异体免疫。
DOI：
10.1111/trf.16224
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发表时间：
2021-03
期刊：
影响因子：
2.9
通讯作者：
Zimring JC
中科院分区：
文献类型：
--
作者：
Poston JN;Jash A;Hannan LM;Hay AM;Usaneerungrueng C;Howie HL;Kapp LM;Zimring JC
血小板输注仍然是许多血小板减少症患者的主要治疗方法，但可能导致人类白细胞抗原（anti-HLA）的同种抗体，导致对后续血小板输注反应不足（难治性），以及使移植复杂化。尽管同种异体免疫随着白细胞的减少而大幅减少，但仍有相当比例的患者在输血小板后产生同种异体免疫。目前尚不清楚为什么有些患者产生抗hla抗体，而有些患者即使长期输血也没有产生抗hla抗体。先前怀孕与人类血小板输注引起的同种异体免疫风险相关——然而，在人群中不可能将怀孕作为单一变量分离出来。通过将C57BL/6 （H-2b）母系与BALB/c （H-2d）母系杂交，构建了小鼠妊娠输血模型。怀孕后，雌性小鼠输注来自F1 （H-2b/d）供体的白细胞诱导的血小板，这些血小板与雄性小鼠表达相同的父系主要组织相容性复合体（MHC） H-2d同种抗原。对照组允许单独将怀孕或输血作为独立变量。同种异体免疫通过检测血清中H-2d MHC同种异体抗原的抗体来确定。单独妊娠后或单独输血小板后未检出同种异体抗体；然而，当怀孕后输血时，检测到显著水平的同种异体抗体。这些发现分离了先前怀孕对小鼠随后血小板输注的同种异体免疫频率增加的因果贡献，并为正在进行的机制研究提供了平台。
Platelet transfusions remain a mainstay of treatment for many patients with thrombocytopenia, but can lead to alloantibodies to Human Leukocyte Antigens (anti-HLA) resulting in inadequate responses to subsequent platelet transfusions (refractoriness), as well as complicate transplantation. Despite substantial decreases in alloimmunization with the implementation of leukoreduction, a significant percentage of patients still become alloimmunized following platelet transfusions. It remains unclear why some patients make anti-HLA antibodies, but others do not make anti-HLA antibodies even with chronic transfusion. Antecedent pregnancy correlates with risk of alloimmunization due to platelet transfusion in humans - however, isolation of pregnancy as a single variable is not possible in human populations. A tractable murine model of pregnancy and transfusion was engineered by breeding C57BL/6 (H-2b) dames with BALB/c (H-2d) sires. After pregnancy, female mice were transfused with leukoreduced platelets from F1 (H-2b/d) donors that expressed the same paternal major histocompatibility complex (MHC) H-2d alloantigens as the sires. Control groups allowed isolation of pregnancy or transfusion alone as independent variables. Alloimmunization was determined by testing serum for antibodies to H-2d MHC alloantigens. No alloantibodies were detected after pregnancy alone, or in response to transfusion of platelets alone; however, significant levels of alloantibodies were detected when pregnancy was followed by transfusion. These findings isolate antecedent pregnancy as a causal contribution to increased frequencies of alloimmunization by subsequent platelet transfusion in mice and provide a platform for ongoing mechanistic investigation.
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