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: 10470880
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470880
• 关键词: Address; Adverse effects; African American; African ancestry; 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.

抽象的 红细胞输注仍然是镰状细胞病（SCD）患者的挽救生命的疗法。一个专业 问题是同种免疫（针对输血红细胞的抗体形成）发生率很高。 患有 SCD 的输血患者。同种免疫导致护理延误、增加成本并导致输血 对于某些患者来说，治疗不安全且不可能。 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 非洲人后裔导致了 SCD 患者抗体的高发生率和复杂性。 我们小组和其他人最近进行的研究表明，患者和捐赠者的 RH 遗传变异是一个 导致Rh同种免疫的主要危险因素。常规血库检测无法识别这些变异，因此 尽管Rh 匹配的红细胞被输注给SCD 患者，但它们只有与Rh 匹配的才是真正的Rh 匹配。 基于 DNA 的匹配。 RH 位点供体单位的基因匹配可能会阻止 Rh 同种异体免疫，但不会 已进行临床试验。主要障碍是当前 RH 基因分型的成本以及库存 供体基因型的数据管理，以确定患者的 RH 匹配单位。此次活动的主要目标 建议进行试点临床研究，为长期输血提供 RH 基因型匹配的红细胞 患有 SCD 的患者。我们将确定在实际中识别足够的基因型匹配供体单位的可行性 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 这个提议是应用新技术来提高我们对两个 RH 基因 RHD 和 RHCE 的了解， 由于其高度的序列相似性，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。在此应用中，我们提出了三个 综合目标可以解决当前 SCD 输血治疗的挑战，并将推动该领域的发展 通过为当前的这些障碍提供创新的解决方案来推动发展。