Donor and unit factors associated with recipient RBC alloimmunization formation

与受者红细胞同种免疫形成相关的供者和单位因素

• 批准号: 10515205
• 负责人: Ronald G. Hauser
• 金额: $ 12.56万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515205
• 关键词: Age; Alloimmunization; Antibodies; Antibody Formation; Antigens; Autoimmunity; Base Ratios; Blood; Blood Banks; Blood Donations; Blood Transfusion; Blood donor; Case-Control Studies; Categories; Characteristics; Chemicals; Communities; Complex Analysis; Cooley' s anemia; Dangerousness; Data; Data Set; Databases; Development; Diagnosis; Disease; Dysmyelopoietic Syndromes; Electronic Health Record; Erythrocyte Transfusion; Erythrocytes; Ethnic Origin; Event; Exposure to; Fetus; Funding; Goals; Health; Hospitals; Human; Incidence; Individual; Inpatients; Institution; Isoantibodies; Link; Modeling; Morbidity - disease rate; Mus; National Heart, Lung, and Blood Institute; Newborn Infant; Odds Ratio; Outcome; Outpatients; Patients; Pregnancy; Prevalence; Public Health; Race; Reaction; Research Design; Risk; Safety; Science; Services; Sickle Cell Anemia; Smoking History; Time; Transfusion; United States; Veins; Whole Blood; antibody detection; case control; cell injury; clinically significant; high risk; innovation; interest; irradiation; mortality; patient population; secondary analysis; sex; time interval

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.

红细胞（RBC）同种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，造成溶血反应等不良后遗症。同种免疫发生于 高达 40% 的某些患者群体，包括镰状细胞病 (SCD) 患者；患者的比率 骨髓增生异常综合征、重型地中海贫血和自身免疫性疾病的发病率也很高。大多数红细胞研究 迄今为止的同种免疫侧重于发病率/患病率和接受者特征/诊断， 很少有研究评估献血者或血液单位对红细胞同种抗体形成的贡献。 美国国家心肺血液研究所 (NHBLI) 资助的 REDS-III 静脉间数据集，可用于 通过 BioLINCC 公开使用，为评估不同接受者的红细胞同种抗体提供了独特的机会 跨多个机构并调查参与输血的潜在献血者和单位变量 相关同种抗体的形成。该数据集包含住院和门诊电子健康 来自美国 4 个主要血液中心以及 12 个社区和学术医院的信息，超过 2013年至2017年为期4年。对该数据集的查询显示，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，在此期间大多数 预计会形成抗体。当前提案的创新在于独特的链接能力 献血者和血液单位特征对 RBC 后同种免疫受者结果的影响 输血。 小鼠研究表明，输血后红细胞清除速度越快，血红蛋白浓度越高。 红细胞同种免疫程度，无论清除率增加是否是由于储存时间较长所致 持续时间或其他原因。因此，我们假设与红细胞储存不良相关的因素 人类，包括红细胞储存时间、供者性别或辐射，将影响同种抗体的可能性 形成。我们建议完成一个病例：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。通过本研究设计，我们建议： 目标 1) 调查献血者 与输血受者红细胞同种免疫相关的特征和目标 2) 研究红细胞 与输血受者红细胞同种免疫相关的单位特征。 从长远来看，与同种免疫相关的任何献血者或红细胞单位特征都可以修改为 红细胞单位适用于红细胞同种免疫风险最高的患者。如果新的抗体能够形成 最小化，输血安全性将会提高。