IMMUNOLOGICAL MECHANISMS OF NEPHRITIS IN CHILDHOOD SLE

描述：（改编自研究者摘要）：儿童全身性 红斑狼疮（SLE）与成人疾病的不同之处在于 肾炎的发病率。研究人员假设， 肾炎的流行是由于几种类型的致肾炎自身抗体 与儿童期SLE同时发生。两个主要候选人 这些自身抗体是针对dsDNA的抗体， 被认为在成人狼疮肾炎和自身抗体中起作用， 核糖体“P”蛋白，以前没有报道， 患有狼疮性肾炎的人除了最近的初步调查 临床和动物数据支持抗P抗体在狼疮性肾炎中的作用， 已经发现抗dsDNA和抗核糖体“P”抗体都含有 在培养中直接结合和损伤细胞的亚群。根据 研究人员认为，这种抗体介导的体外细胞损伤现象可能是 它们在体内的免疫致病潜力的替代物。调查人员 建议定义个体中自身抗体的致病潜力 患者通过亲和纯化他们的自身抗体和研究他们的 与培养物中各种细胞类型的相互作用以及对细胞功能的影响 和生存能力。在初步研究中，他们复制了以前的工作， 显示一些人类抗dsDNA抗体通过补体损伤细胞， 依赖于细胞表面的机制，以及其他穿透细胞的机制， 定位于细胞核或细胞质，像抗P， 蛋白质合成研究人员将把这些免疫致病因素 体外性质与患者的临床状态。他们提议扩大 他们的研究独特型调节这些抗体的患者， 抗P抗体对成人的平行研究表明，与儿童一样， 抗dsDNA和抗P抗体的存在大大增加了 活动性肾炎调查人员还初步数据表明，抗P可能 在人肾小球洗脱液中富集，并建议扩大这些研究。 最后，他们建议开发一种动物模型来评估致肾炎性 诱导抗P抗体的可能性。他们希望这些研究能够 扩大对儿童肾炎免疫发病机制的看法， 成人SLE

DESCRIPTION: (Adapted from the Investigator's abstract): Childhood systemic lupus erythematosus (SLE) differs from the disease in adults by a higher prevalence of nephritis. The investigators hypothesize that this higher prevalence of nephritis is due to several types of nephritogenic autoantibodies that occur concurrently in the childhood form of SLE. Two major candidates for these autoantibodies are those directed against dsDNA which have long been recognized to play a role in adult lupus nephritis and autoantibodies to ribosomal "P" protein which have not been reported previously to be associated with either adult or pediatric lupus nephritis. Aside from recent preliminary clinical and animal data that support a role for anti-P in lupus nephritis, both anti-dsDNA and anti-ribosomal "P" antibodies have been found to contain subsets that directly bind and injure cells in culture. According to the investigators, this antibody-mediated, in vitro cell injury phenomenon could be a surrogate for their immunopathogenic potential in vivo. The investigators propose to define the pathogenic potential of the autoantibodies in individual patients by affinity purifying their autoantibodies and by studying their interaction with various cell types in culture and the effects on cell function and viability. In preliminary studies, they have reproduced previous work by showing that some human anti-dsDNA antibodies injure cells by a complement dependent mechanism at the cell surface, and others penetrate the cell, localize in either the nucleus or the cytoplasm, and like anti-P, inhibit protein synthesis. The investigators will correlate these immunopathogenetic properties in vitro with the patients' clinical status. They propose to expand their studies of the idiotypic regulation of these antibodies in patients with anti-P antibodies. Parallel studies in adults suggest that, like children, the presence of both anti-dsDNA and anti-P antibodies greatly increase the risk of active nephritis. The investigators also have preliminary data that anti-P may be enriched in human glomerular eluates and propose to expand these studies. Lastly, they propose to develop an animal model to assess the nephritogenic potential of induced anti-P antibodies. They hope that these studies would expand perspectives on the immunopathogenesis of nephritis in both children and adults with SLE.