Alloantibodies to a paternally derived RBC KEL antigen lead to hemolytic disease of the fetus/newborn in a murine model.
Alloantibodies to a paternally derived RBC KEL antigen lead to hemolytic disease of the fetus/newborn in a murine model.
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DOI：
10.1182/blood-2013-03-488874
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发表时间：
2013-08
期刊：
影响因子：
20.3
通讯作者：
S. Stowell;Kate L. Henry;Nicole H. Smith;K. Hudson;G. Halverson;Jaekeun C. Park;Ashley Bennett;K. Girard-Pierce;C. Arthur;S. Bunting;J. Zimring;J. Hendrickson
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文献类型：
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作者：
S. Stowell;Kate L. Henry;Nicole H. Smith;K. Hudson;G. Halverson;Jaekeun C. Park;Ashley Bennett;K. Girard-Pierce;C. Arthur;S. Bunting;J. Zimring;J. Hendrickson
暴露于非自身红细胞（RBC）抗原，无论是输血或妊娠，可能会导致同种异体免疫和不相容的RBC清除。胎儿和新生儿溶血性疾病（HDFN）在80年前首次被描述为妊娠并发症，是由对父系来源的RBC抗原的同种免疫引起的。尽管HDFN的发病率/死亡率高，但RBC同种免疫风险的女性几乎没有治疗选择。鉴于KEL家族中抗原的同种抗体是最具临床意义的，我们开发了一种具有RBC特异性表达人KEL抗原的小鼠模型，以评估母体/胎儿KEL不相容性的影响。在与KEL阳性雄性小鼠连续妊娠期间暴露于胎儿KEL RBC后，21/21只野生型雌性小鼠产生了抗KEL同种抗体;在野生型KEL阳性幼仔的一个亚组中发生了宫内胎儿贫血和/或死亡，但无丙种球蛋白血症母亲未发生。与之前在人类中的观察结果相似，妊娠相关同种抗体在输血环境中是有害的，而输血相关同种抗体在妊娠环境中是有害的。这是迄今为止描述的第一个妊娠相关HDFN模型，它将作为开发靶向治疗的平台，以预防和/或减轻RBC同种抗体对胎儿和新生儿的危险。
Exposure to nonself red blood cell (RBC) antigens, either from transfusion or pregnancy, may result in alloimmunization and incompatible RBC clearance. First described as a pregnancy complication 80 years ago, hemolytic disease of the fetus and newborn (HDFN) is caused by alloimmunization to paternally derived RBC antigens. Despite the morbidity/mortality of HDFN, women at risk for RBC alloimmunization have few therapeutic options. Given that alloantibodies to antigens in the KEL family are among the most clinically significant, we developed a murine model with RBC-specific expression of the human KEL antigen to evaluate the impact of maternal/fetal KEL incompatibility. After exposure to fetal KEL RBCs during successive pregnancies with KEL-positive males, 21 of 21 wild-type female mice developed anti-KEL alloantibodies; intrauterine fetal anemia and/or demise occurred in a subset of KEL-positive pups born to wild type, but not agammaglobulinemic mothers. Similar to previous observations in humans, pregnancy-associated alloantibodies were detrimental in a transfusion setting, and transfusion-associated alloantibodies were detrimental in a pregnancy setting. This is the first pregnancy-associated HDFN model described to date, which will serve as a platform to develop targeted therapies to prevent and/or mitigate the dangers of RBC alloantibodies to fetuses and newborns.