IMMUNE MECHANISMS OF ANTICD40L TRIAL IN SLE

描述（逐字摘自研究者摘要）：我们的主要目的 是研究治疗的基本免疫机制， 人源化抗CD 40配体抗体（抗CD 40 L，BG 9588）的作用 狼疮性肾炎的症状有哪些？共约 来自28个中心的120名患者参与了这项随机、双 申办的抗CD 40 L（BG 9588）设盲、对照、多次给药研究 关于Biogen Inc. CD 40 L和CD 40之间的分子相互作用提供了 体液和细胞免疫的必需共刺激信号 应答最值得注意的是，T型和B型狼疮高表达CD 40 L 细胞异常延长的时间-从而维持生产 致病性自身抗体此外，一个简短的治疗三- 在一周内向狼疮小鼠注射抗CD 40 L可以防止 肾炎的发展超过一年。这种机制 长期受益，相当于人类的3-4年， 未知这项临床试验提供了前所未有的机会， 研究抗CD 40 L对人体免疫系统的影响， 特别是对参与慢性持续性 狼疮患者的自身免疫反应我们将研究 自身免疫性T和B细胞参与产生 治疗前、治疗中和治疗后的病原性抗核自身抗体 回答以下问题：一。是自身免疫性T细胞， 特别是那些对核小体肽有反应并驱动 致病性抗DNA自身抗体的产生，缺失或无反应 抗CD 40 L治疗的患者中，？二.是狼疮的自身免疫B细胞 产生致病性自身抗体的核小体特异性基因， 还是抗CD 40 L治疗导致无反应三.是调节性T细胞 是否可以抑制抗CD 40 L治疗产生的自身抗体？ 我们希望更多地了解正常和狼疮免疫系统的工作原理， 这些研究中的人类系统。

DESCRIPTION (Verbatim from Investigator's abstract): Our main objective is to study the basic immunologic mechanisms underlying the therapeutic effects of a humanized anti-CD40 ligand antibody (anti-CD40L, BG9588) administered into patients with active lupus nephritis. A total of about 120 patients in 28 centers are participating in this randomized, double- blind, controlled, multiple-dose study of anti-CD40L (BG9588) sponsored by Biogen Inc. Molecular interactions between CD40L and CD40 provides essential costimulatory signals for humoral and cellular immune responses. Most remarkably, CD40L is hyperexpressed by lupus T and B cells for abnormally prolonged periods -- thus sustaining the production of pathogenic autoantibodies. Moreover, a brief therapy of three- injections of anti-CD40L in one week into lupus mice prevents the development of nephritis for more than a year. The mechanism of such a long-term benefit, which is equivalent to 3-4 decades in humans, is unknown. This clinical trial provides an unprecedented opportunity to study the effects of anti-CD40L on the human immune system in vivo, particularly on the cells participating in the chronic ongoing autoimmune response in lupus patients. We will study the status of autoimmune T and B cells that are involved in the production of pathogenic anti-nuclear autoantibodies, before, during and after therapy to answer the following questions: I. Are autoimmune T cells, particularly the ones that respond to nucleosomal peptides and drive the production of pathogenic anti-DNA autoantibodies, deleted or anergized in the anti-CD40L treated patients? II. Are autoimmmune B cells of lupus that make pathogenic autoantibodies and are nucleosome-specific, deleted or anergized by anti-CD40L therapy? III. Are regulatory T cells that could suppress autoantibody production, generated by anti-CD40L therapy? We expect to know more about the workings of the normal and lupus immune systems in humans from these studies.