IMMUNOMODULATION FOLLOWING TRANSFUSION

输血后的免疫调节

基本信息

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
项目类别：
财政年份：
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

项目摘要

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共释放到HLA蛋白的同种异体。用红细胞（RBC）和血小板（PIT）和广泛的免疫抑制输血。虽然已经提出了血液成分的白细胞来减少敏感性，没有足够的可用于预测其受益者受益的数据，这些受益者未通过恶性肿瘤或化学疗法进行免疫抑制。拟议的研究是一项三臂随机试验，接受了接受标准血液产品的接受者，白细胞的血液产物（LR）或已被伽玛辐照的血液产物（LRG）。本研究中的免疫能力患者是接受心脏手术的患者因为输血支持是通过暴露于4-10个同种异体供体的情况下的。抗使用流式细胞仪输血后的3点，接受者的HLA抗体将测量。研究测试输血是免疫抑制的假设已经测量了临床结果：结肠癌的复发，术后感染的发病率或住院时间。有关于输血对受体免疫调节细胞的影响的数据很少。这些研究将衡量影响对两个受体调节T细胞的输血：NKT和CD4+ Treg。流式细胞仪表型将用于比较每个个体输血之前和之后的这些人群。调节基因的细胞因子表型和表达（FOXP，GITR，CTLA4）将使用流量测量细胞仪，ELISPOT和实时PCR。与将确定收件人。我们还将直接比较产生TGF-的单核细胞的数量手术前后收集的样品中的β作为免疫抑制的替代量度。这些研究将提供有关输血后特定免疫调节结果的数据。数据也将提供敏化率，以指导免疫能力患者的输血成分的选择。