Donor and unit factors associated with recipient RBC alloimmunization formation

红细胞(RBC)异体免疫是输血和输血中发病率和死亡率的主要原因。 妊娠环境，导致溶血反应等不良后遗症。同种异体免疫发生在 高达40%的某些患者群体，包括那些患有镰状细胞病(SCD)的患者； 骨髓增生异常综合征、重型地中海贫血和自身免疫性贫血也很高。大多数关于RBC的研究 到目前为止，免疫接种的重点是发病率/流行率和受者特征/诊断， 很少有研究评估献血者或血液单位对红细胞同种异体抗体形成的贡献。 国家心肺血液研究所(NHBLI)资助的REDS-III静脉到静脉数据集，可用于 通过BioLINCC公开使用，为评估不同受者的红细胞同种异体抗体提供了独特的机会 跨多个机构，并调查潜在的献血者和输血单位变量 相关同种异体抗体的形成。该数据集包含住院患者和门诊患者的电子健康 来自美国四大血液中心和12家社区和学术医院的信息，超过 2013年至2017年的4年时间段。对数据集的查询显示，有651名受试者具有新的 红细胞抗体是在输血后的15天至16周内形成的，大多数 预计会形成抗体。目前方案的创新之处在于独特的链接能力 献血者和血液单位特征对RBC后异基因免疫受者结局的影响 输血。 小鼠研究表明，输血后红细胞清除更快与更高的 红细胞同种异体免疫程度，无论这种清除增加是否是由于储存时间更长 持续时间或其他原因。因此，我们假设与较差的RBC存储相关的因素 人类，包括红细胞储存时间、供者性别或辐射，将影响同种异体抗体的可能性。 队形。我们建议完成一项病例：对照(1：4)研究，将病例和对照按年龄、性别、 诊断、种族和民族。根据本研究设计，我们建议：1)调查献血者 输血受者红细胞同种异体免疫的特点和目的2)调查红细胞 输血受者中与红细胞同种异体免疫相关的单位特征。 从长远来看，任何与异基因免疫相关的献血者或红细胞单位特征都可以被修改为 红细胞单位适用于红细胞同种异体免疫风险最高的患者。如果新抗体的形成 最大限度地减少，输血的安全性将会增加。

Red blood cell (RBC) alloimmunization is a leading cause of morbidity and mortality in transfusion and pregnancy settings, resulting in hemolytic reactions and other adverse sequelae. Alloimmunization occurs in up to 40% of some patient populations, including those with sickle cell disease (SCD); rates in patients with myelodysplastic syndrome, thalassemia major, and autoimmunity are also high. Most studies of RBC alloimmunization to date have focused on incidence/prevalence rates and recipient characteristics/diagnoses, and few studies have evaluated blood donor or blood unit contributions to RBC alloantibody formation. The National Heart, Lung, and Blood Institute (NHBLI) funded REDS-III vein-to-vein data set, available for public use through BioLINCC, allows a unique opportunity to evaluate RBC alloantibodies in diverse recipients across multiple institutions and to investigate potential blood donor and unit variables involved in transfusion associated alloantibody formation. This data set contains inpatient and outpatient electronic health information from four major blood centers and 12 community and academic hospitals in the United States, over a 4-year time-period from 2013-2017. A query of the data set has shown that there are 651 subjects with a new RBC antibody formed in the time interval (15 days to 16 weeks) following transfusion over which most antibodies would be expected to form. The innovation of the current proposal lies in the unique ability to link blood donor and blood unit characteristics to the recipient outcome of alloimmunization following RBC transfusion. Murine studies have shown that more rapid RBC clearance following transfusion is associated with a higher degree of RBC alloimmunization, regardless of whether that increased clearance is due to longer storage duration or other causes. As such, we hypothesize that factors associated with poorer RBC storage in humans, including red cell storage duration, donor sex, or irradiation, will impact the likelihood of alloantibody formation. We propose to complete a case: control (1:4) study, matching cases and controls for age, sex, diagnosis, race, and ethnicity. With this study design, we propose: Aim 1) To investigate blood donor characteristics associated with RBC alloimmunization in transfusion recipients and Aim 2) To investigate RBC unit characteristics associated with RBC alloimmunization in transfusion recipients. Long term, any blood donor or RBC unit characteristic associated with alloimmunization could be modified for RBC units intended for patients at highest risk of RBC alloimmunization. If new antibody formation could be minimized, transfusion safety will increase.