MODIFICATION OF ALLOIMMUNITY BY IVIG IN ESRD PATIENTS

IVIG 对 ESRD 患者同种免疫的改变

• 批准号: 2672818
• 负责人: STANLEY C JORDAN
• 金额: $ 42.47万
• 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 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672818
• 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：本申请提出解决高架桥的问题。 细胞毒性抗体，阻止个体成功地 交叉配血进行移植 研究的主要目的是 在这些高度致敏的患者中， 减少肾移植的等待时间和 严重排斥和移植物丢失。 这项研究是基于这样的假设， 给予合并的人静脉注射丙种球蛋白（IVIG）将减少 抗HLA抗体活性和减少同种异体致敏后， 移植 申请人提供了来自其实验室和 其他人强烈表明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 并可能提高同种异体移植物存活率。 申请人提出了一项双盲、随机对照临床试验， IVIG与安慰剂在100例高度HLA致敏成人患者中的试验 终末期肾病（ESRD），等待肾移植。 等待移植的患者将接受三种IVIG治疗， 移植前安慰剂和移植后三种治疗。 该试验将确定IVIG是否上级安慰剂：（1）降低 抗HLA抗体滴度和同种异体反应性的其他测量，（2）降低 等待移植的时间;（3）提高移植存活率。