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：此应用程序建议解决提升的问题 阻止个体成功的细胞毒性抗体 用于移植的交叉配型。研究的主要目的是 在这些高度致敏的患者中依次降低抗-HLA抗体效价 减少肾移植的轮候时间和发病率 严重的排斥反应和移植物丢失。这项研究是基于这样一个假设： 人静脉注射丙种球蛋白(IVIG)将减少 抗人类白细胞抗原抗体活性及降低同种异体致敏作用 移植。申请者提交来自其实验室和来自 其他强烈表明IVIG含有独特型抗-抗-HLA的人 具有抑制抗人类白细胞抗原抗体细胞毒作用的抗体 在体外和体内，并可能提高同种异体移植物的存活率。 申请人提出一项双盲随机对照临床试验。 静脉注射免疫球蛋白与安慰剂治疗100例高度致敏成人慢性阻塞性肺疾病的对照研究 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 移植前服用安慰剂，移植后进行三种治疗。 这项试验将确定静脉注射免疫球蛋白是否在以下方面优于安慰剂：(1)降低 抗人类白细胞抗原抗体滴度和其他同种异体反应性的测量，(2)降低 等待移植时间；(3)提高移植存活率。