Donor and unit factors associated with recipient RBC alloimmunization formation

红细胞（RBC）同种异体免疫是输血中发病和死亡的主要原因， 妊娠环境，导致溶血反应和其他不良后遗症。同种异体免疫发生在 高达40%的患者人群，包括镰状细胞病（SCD）患者; 骨髓增生异常综合征、重型地中海贫血和自身免疫也很常见。大多数RBC研究 迄今为止，同种免疫接种的重点是发病率/流行率和接受者特征/诊断， 并且很少有研究评估血液供体或血液单位对RBC同种抗体形成的贡献。 国家心肺血液研究所（NHBLI）资助的REDS-III静脉-静脉数据集，可用于 通过BioLINCC公开使用，为评估不同受者的RBC同种抗体提供了独特的机会 在多个机构，并调查潜在的献血者和单位变量涉及输血 相关同种抗体形成。此数据组包含住院病人和门诊病人电子健康 来自美国四个主要血液中心和12个社区和学术医院的信息， a 2013 - 2017年4年。对数据集的查询显示，有651名受试者具有新的 红细胞抗体在输血后的时间间隔（15天至16周）内形成，在此期间， 预计会形成抗体。当前提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红细胞移植后同种异体免疫受者结局的影响 输血 小鼠研究表明，输血后更快的RBC清除与更高的 RBC同种异体免疫程度，无论清除率增加是否由于储存时间延长 时间或其他原因。因此，我们假设，与红细胞储存较差相关的因素， 人类，包括红细胞储存时间，供体性别或照射，将影响同种抗体的可能性 阵我们建议完成病例：对照（1：4）研究，匹配病例和对照的年龄、性别， 诊断，种族和民族。本研究的目的：1）调查献血者 输血受者红细胞同种异体免疫的特点及目的 输血受者红细胞同种异体免疫相关的单位特征 从长远来看，任何与同种异体免疫相关的献血者或RBC单位特征都可以被修改， RBC单位预期用于RBC同种异体免疫风险最高的患者。如果新的抗体形成可以 最小化，输血安全性将增加。

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.