IMMUNOMODULATION FOLLOWING TRANSFUSION

与输血相关的并发症包括白细胞上HLA蛋白的同种异体免疫， 输注红细胞（RBC）和血小板（PIT）以及全身免疫抑制。虽然 已经提出减少血液成分的白细胞以使同种异体致敏最小化，但还存在不足。 可获得的数据来预测其在未受到恶性肿瘤或化疗的免疫抑制的受者中的益处。 这项研究是一项三组随机试验，受试者接受标准血液制品， 白细胞减少的血液制品（LR），或经伽马辐照的白细胞减少的血液制品（LRG）。 本研究中的免疫功能正常的患者是那些接受心脏手术的患者， 因为输血支持被明确定义为接触4-10个同种异体供体。生产抗- 在输血后3个时间点用流式细胞术检测受者的HLA抗体。研究 测试输血是免疫抑制的假设已经测量了临床结果： 结肠癌复发、术后感染发生率或住院时间。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 输血对两种受体调节性T细胞群体的影响：NKT和CD 4 + Treg。流式细胞术 表型分析将用于比较每个个体输血前后的这些群体。 将使用流式细胞仪测量细胞因子表型和调节基因（FoxPS、GITR、CTLA 4）的表达 细胞术、ELISPOT和实时PCR。与供体共享HLA II类表位的供体的数量 收件人将被确认。我们还将直接比较产生TGF-β的单核细胞的数量， 作为免疫抑制的替代测量，在手术前后收集的样品中的β。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血成分。

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.