RH genotype matched red cell transfusions for patients with sickle cell disease

镰状细胞病患者 RH 基因型匹配的红细胞输注

• 批准号: 10259737
• 负责人: STELLA T CHOU
• 金额: $ 83.48万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259737
• 关键词: Address; Adverse effects; African; African American; Alleles; Alloimmunization; Antibodies; Antibody Formation; Antigens; Biological Assay; Blood; Blood Banks; Blood donor; Blood group antibody D; Caring; Cells; Chronic; Clinical; Clinical Research; Clinical Trials; Collaborations; Complex; Complication; Custom; D Cells; DNA; Donor Selection; Effectiveness; Equipment and supply inventories; Erythrocyte Transfusion; Erythrocytes; Event; Exposure to; Frequencies; Gene Duplication; Gene Family; Gene Frequency; Genes; Genetic; Genetic Heterogeneity; Genetic Recombination; Genetic Variation; Genotype; Goals; Hemolysis; Hospitals; Hybrids; Incidence; Individual; Institution; Knowledge; Lead; Life; Methods; Minority; Modeling; Monitor; Morbidity - disease rate; Multicenter Studies; Patient Care; Patient Monitoring; Patients; Phase; Phenotype; Prospective Studies; Proteins; Recording of previous events; Research Personnel; Rh-Hr Blood-Group System; Risk Factors; Safety; Savings; Serology; Services; Sickle Cell Anemia; System; Technology; Transfusion; Variant; Visit; base; bench to bedside; clinical practice; clinically significant; cohort; cost; cost effective; data management; design; effectiveness evaluation; feasibility testing; genetic variant; improved; innovation; new technology; next generation sequencing; novel; novel sequencing technology; precision medicine; prevent; prophylactic; prospective; recruit

ABSTRACT Red blood cell transfusion remains a life-saving therapy for patients with sickle cell disease (SCD). A major problem is the high rate of alloimmunization (antibody formation against transfused red cells) that occurs in transfused patients with SCD. Alloimmunization leads to delays in care, increases costs, and makes transfusion therapy unsafe and impossible for some patients. The most common antibodies formed by patients with SCD are directed against the Rh blood group system. Genetic diversity in Rh antigens in patients and blood donors of African descent contributes to this high incidence and complexity of antibodies found in patients with SCD. Recent studies performed by our group and others demonstrate RH genetic variants in patients and donors is a major risk factor leading to Rh alloimmunization. Routine blood bank assays can not identify these variants, so although Rh-matched red cells are transfused to patients with SCD, they would only be truly Rh-matched with DNA-based matching. Genetic matching of donor units at the RH loci may prevent Rh alloimmunization but no clinical trials have been conducted. Major barriers are the current cost of RH genotyping as well as inventory and data management of donor genotypes to identify RH matched units for patients. The major goal of this proposal is to perform pilot clinical studies to provide RH genotype matched red cells to chronically transfused patients with SCD. We will determine the feasibility of identifying adequate genotype matched donor units in real clinical practice, identify barriers, and prospectively monitor patients for Rh alloimmunization. A second goal for this proposal is to apply new technologies to improve our knowledge of the two RH genes, RHD and RHCE, which due to their high sequence similarity, currently makes it challenging to apply low cost sequencing methods to provide RH genotype matched red cells for all patients with SCD. In this application, we propose three integrated aims that can address the current challenges of transfusion therapy for SCD, and will drive the field forward by providing innovative solutions to these current obstacles.

摘要 红细胞输注仍然是镰状细胞病（SCD）患者的救命疗法。一个主要 问题是发生在体内的同种免疫（针对输注红细胞的抗体形成）的高比率， 输血的SCD患者。同种免疫导致护理延迟，增加成本，并使输血 治疗对某些患者来说是不安全和不可能的。SCD患者形成的最常见抗体 是针对Rh血型系统的。患者和献血者Rh抗原的遗传多样性 非裔美国人导致SCD患者中发现的抗体的高发病率和复杂性。 我们小组和其他人最近进行的研究表明，患者和供体的RH遗传变异是一个重要因素。 导致Rh同种异体免疫的主要危险因素。常规的血库检测无法识别这些变异， 尽管Rh匹配的红细胞被输注给SCD患者，但它们只有与Rh匹配的红细胞才是真正的Rh匹配。 DNA匹配供体单位在RH基因座的遗传匹配可能会阻止Rh同种免疫，但不会 已经进行了临床试验。主要障碍是目前RH基因分型的成本以及库存 和供体基因型的数据管理，以确定患者的RH匹配单位。这个项目的主要目标是 建议进行试点临床研究，以提供RH基因型匹配的红细胞，以长期输血 SCD患者我们将确定在真实的中鉴定足够的基因型匹配的供体单位的可行性。 临床实践，识别障碍，并前瞻性监测患者的Rh同种免疫。第二个目标是 该建议是应用新技术来提高我们对两个RH基因RHD和RHCE的认识， 由于它们的高序列相似性，目前使得应用低成本测序方法具有挑战性 为所有SCD患者提供RH基因型匹配的红细胞。在本申请中，我们提出三个 整合的目标，可以解决目前面临的挑战，输血治疗SCD，并将推动该领域 通过提供创新的解决方案来解决这些现有的障碍。