MODIFICATION OF ALLOIMMUNITY BY IVIG IN ESRD PATIENTS

IVIG 对 ESRD 患者同种免疫的改变

• 批准号: 2887253
• 负责人: STANLEY C JORDAN
• 金额: $ 44.17万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887253
• 关键词: antiidiotype antibody; artificial immunosuppression; chronic renal failure; clinical research; clinical trials; cooperative study; drug screening /evaluation; enzyme linked immunosorbent assay; gamma globulin; histocompatibility; histocompatibility antigens; human subject; human therapy evaluation; intravenous administration; kidney transplantation; postoperative state; preoperative state; prognosis; serology /serodiagnosis; statistics /biometry; transplant rejection; transplantation immunology

DESCRIPTION: This application proposes to address the problem of elevated cytotoxic antibodies that precludes individuals from being successfully crossmatched for transplantation. The main objective of the study is to lower anti-HLA antibody titers in these highly sensitized patients in order to reduce the waiting time for kidney transplantation and the incidence of severe rejection and graft loss. The study is based on the hypothesis that administration of pooled human intravenous gamma globulin (IVIG) will reduce anti-HLA antibody activity and reduce allosensitization after transplantation. The applicants present data from their laboratory and from others that strongly suggest that IVIG contains idiotypic anti-anti-HLA antibodies which have the capacity to inhibit anti-HLA antibody cytotoxicity in vitro and in vivo, and possibly enhance allograft survival. The applicants propose a double-blinded, randomized controlled clinical trial of IVIG vs placebo in 100 highly HLA sensitized adult patients with End-Stage Renal Disease (ESRD) that are awaiting kidney transplantation. Patients awaiting transplantation will receive three treatments of IVIG or placebo prior to transplantation and three treatments post-transplantation. The trial will determine if IVIG is superior to placebo in: (1) lowering anti-HLA antibody titers and other measures of alloreactivity, (2) reducing waiting time to transplantation, and (3) improving transplant survival.

描述：该应用旨在解决升高的问题 细胞毒性抗体阻碍个体成功 交叉配型用于移植。 该研究的主要目的是 在这些高度敏感的患者中降低抗 HLA 抗体滴度，以便 减少肾移植的等待时间和发生率 严重排斥反应和移植物丢失。 该研究基于以下假设： 混合人静脉注射丙种球蛋白 (IVIG) 的施用将减少 抗 HLA 抗体活性并减少术后异体敏化 移植。 申请人提供了来自其实验室和来自 其他强烈表明 IVIG 含有独特型抗抗 HLA 具有抑制抗HLA抗体细胞毒性能力的抗体 体外和体内，并可能提高同种异体移植物的存活率。 申请人提出了一项双盲、随机对照临床研究 在 100 名 HLA 高度敏感的成人患者中进行 IVIG 与安慰剂的试验 正在等待肾移植的终末期肾病（ESRD）。 等待移植的患者将接受三种 IVIG 或 移植前安慰剂和移植后三种治疗。 该试验将确定 IVIG 在以下方面是否优于安慰剂：(1) 降低 抗 HLA 抗体滴度和其他同种反应性指标，(2) 减少 移植的等待时间，以及（3）提高移植存活率。