IMMUNOMODULATION FOLLOWING TRANSFUSION

输血后的免疫调节

• 批准号: 7689742
• 负责人: KAREN A NELSON
• 金额: $ 55.57万
• 依托单位: BLOODWORKS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7689742
• 关键词: Affect; Allogenic; Alloimmunization; Animal Model; Antibodies; Antibody Formation; Antigen Receptors; Antigen-Presenting Cells; Apoptotic; Attention; Autoimmune Diseases; Autoimmunity; B-Cell Activation; Biological Assay; Blood; Blood Platelets; Blood Transfusion; Blood and Blood Products; Blood donor; Blood specimen; CD4 Positive T Lymphocytes; CTLA4 gene; Cardiac Surgery procedures; Cell Lineage; Cell physiology; Cell surface; Cells; Cellular Immunity; Class; Clinical; Clinical Research; Cohort Studies; Collecting Cell; Colon Carcinoma; Complement; Complication; Condition; Data; Dendritic Cells; Doctor of Medicine; Donor person; Down-Regulation; Effector Cell; Elements; Epitopes; Erythrocytes; Exposure to; Flow Cytometry; HLA Antigens; HLA-DR Antigens; Haplotypes; Health Care Costs; Healthcare; Hospitalization; Human; IL2RA gene; Immune; Immune response; Immunity; Immunocompetent; Immunoglobulin G; Immunoglobulin M; Immunologics; Immunosuppression; Immunosuppressive Agents; Incidence; Individual; Infection; Inflammatory; Interleukin-10; Isoantibodies; Kidney Transplantation; Knowledge; Length; Leukocytes; Link; Lymphocyte; Malignant Neoplasms; Measurement; Measures; Mediating; Mononuclear; Neoplasm Metastasis; Normal Cell; Numbers; Operative Surgical Procedures; Outcome; Patient Care; Patients; Peptides; Peripheral; Personal Satisfaction; Phenotype; Platelet Transfusion; Play; Policies; Polymerase Chain Reaction; Population; Postoperative Period; Principal Investigator; Production; Prospective Studies; Proteins; Randomized Controlled Clinical Trials; Range; Rate; Recurrence; Regulator Genes; Reporting; Research; Research Personnel; Rest; Role; Sampling; Sensitivity and Specificity; Severities; Sorting - Cell Movement; Standards of Weights and Measures; T-Lymphocyte; Testing; Therapeutic immunosuppression; Transforming Growth Factor beta; Transfusion; Transplantation; United States Food and Drug Administration; Upper arm; alpha-galactosylceramide; chemotherapy; cohort; cost; cytokine; enzyme linked immunospot assay; human subject; immunoregulation; immunosuppressed; irradiation; kidney allograft; peripheral blood; programs; response; tumor

Complications associated with transfusion include alloimmunization to HLA proteins on leukocytes co- transfused with red cells (rbc) and platelets (pit)and a generalized immunosuppression. Although leukoreduction of blood components has been proposed to minimize allosensitization, there is inadequate data available to predict its benefit in recipients not immunosuppressed by malignancy or chemotherapy. The proposed study is a three arm randomized trial with recipients receiving standard blood products, leukoreduced blood products (LR), or leukoreduced blood products that have been gamma irradiated (LRG). The immunocompetent patients in this study are those undergoing cardiac surgery and were selected because transfusion support is well defined with exposure to 4-10 allogeneic donors. The production of anti- HLA antibody by recipients will be measured at 3 points after transfusion using flow cytometry. Studies testing the hypothesis that transfusions are immunosuppressive have measured clinical outcomes: recurrence of colon carcinoma, incidence of post-operative infection, or length of hospitalization. There is little data on transfusion's effect on recipient immunoregulatory cells. These studies will measure the impact of transfusion on two populations of recipient regulatory T cells: NKT and CD4+ Treg. Flow cytometry phenotyping will be used to compare these populations before and after transfusion in each individual. Cytokine phenotype and expression of regulatory genes (FoxPS, GITR, CTLA4) will be measured using flow cytometry, ELISPOT, and Realtime PCR. The number of donors sharing HLA class II epitopes with the recipient will be identified. We will also directly compare the number of mononuclear cells producing TGF- beta in samples collected prior to and after surgery as a surrogate measure of immunosuppression. These studies will provide data on specific immunoregulatory outcomes following transfusion. The data will also provide sensitization rates to guide selection of transfusion components for immunocompetent patients.

与输血相关的并发症包括对白细胞上的HLA蛋白的同种异体免疫。 输注红细胞(RBC)和血小板(PIT)和全身免疫抑制。虽然 白血球降低血液成分已被提出，以最大限度地减少同种异体致敏，存在不足 现有数据可用于预测其在未因恶性肿瘤或化疗而免疫抑制的受者中的益处。 这项拟议的研究是一项三组随机试验，受试者接受标准血液产品， 降白细胞血液制品(LR)，或经过伽马辐射的降白细胞血液制品(LRG)。 在这项研究中，免疫功能正常的患者是那些接受心脏手术的患者，并被选择 因为输血支持很好地定义为接触4-10名同种异体捐赠者。生产的抗病毒药物 在输血后3个时间点用流式细胞仪检测受者的人类白细胞抗原抗体。研究 对输血具有免疫抑制作用的假设进行了检验，并对临床结果进行了评估： 结肠癌复发、术后感染发生率或住院时间。的确有 关于输血对受体免疫调节细胞影响的数据很少。这些研究将衡量影响 在两组受者调节性T细胞上的输血：NKT和CD4+Treg。流式细胞术 表型分析将被用来比较每个个体在输血前后的群体。 细胞因子表型和调控基因(FoxPS、GITR、CTLA4)的表达将使用FLOW进行检测 流式细胞术、ELISPOT和实时聚合酶链式反应。与人类白细胞抗原II类表位相同的捐赠者数量 收件人的身份将被确认。我们还将直接比较产生转化生长因子-2的单个核细胞的数量。 手术前和手术后采集的样本中的β作为免疫抑制的替代措施。这些 研究将提供输血后特定免疫调节结果的数据。数据还将 提供致敏率，以指导免疫功能正常的患者选择输液成分。