EXPERIMENTAL INDUCTION OF SLE BY ALTERED IA

通过改变 IA 实验诱导 SLE

• 批准号: 3156749
• 负责人: ROBERT A. EISENBERG
• 金额: $ 15.94万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3156749
• 关键词: MHC class II antigen; antibody formation; antinuclear autoantibody; autoantibody; enzyme linked immunosorbent assay; genetic strain; glomerulonephritis; graft versus host disease; immunogenetics; immunoglobulin genes; laboratory mouse; major histocompatibility complex; rheumatoid factor; systemic lupus erythematosus

The current application proposes to investigate the genetic control of autoantibody production in experimental and spontaneous systemic lupus erythematosus in mice. It will concentrate on two genetic loci which play a major role in general immunity: immunoglobulin and major histocompatibility complex. The proposed work is based on previous observations that certain alleles at these loci confer particular susceptibility to autoimmunity. The specific aims are outlined as follows: 1. How does the Igh(b) allotype favor autoantibody production? a. Does the b-allotype effect extend to additional isotypes and autoantibody specificities? b. Is b-allotype skewing specific for autoantibodies? c. Does b-allotype skewing of autoantibodies occur in other strain combinations? d. Does the allotype effect result from the V-region or C-region? e. Is somatic mutation greater in the b allotype than in the a allotype? f. Are there constant region effects? g. Does the light-chain locus also have an effect on autoantibody production? 2. What are the relative roles of I-E version I-A recognition in the autoimmune graft-versus-host reaction (GVH)? a. Are there quantitative differences in I-A versus I-E recognition? b. Are there differences in fine specificity for ANAs induced by disparity at I-E versus I-A? c. Are there differences in glomerulonephritis between I-A- and I-E-mediated GVH disease? d. How is GVH disease down regulated? These proposed studies will further the mechanistic understanding of the genetics of autoimmunity. Such knowledge will help uncover the basic immunoregulatory dysfunctions that produce systemic autoimmunity and will eventually allow the development of rational therapy.

目前的应用程序建议研究基因 实验性和自发性自身抗体产生的控制 小鼠系统性红斑狼疮。它将集中在两个基因上 在全身免疫中起主要作用的基因座：免疫球蛋白和 主要组织相容性复合体。建议的工作是基于以前的 观察到这些基因座上的某些等位基因赋予了特定的 对自身免疫的易感性。具体目标概述如下 以下是： 1.IgH(B)异型如何促进自身抗体的产生？ A.b同种异型效应是否延伸到其他同种异型和 自身抗体的特异性？ B.同种异型偏斜是否是自身抗体所特有的？ C.自身抗体的b型同种异体偏斜是否发生在其他菌株中？ 组合？ 异型效应是由V区还是C区引起的？ B型的体细胞突变比a型的大吗？ 同种异型？ F.是否存在持续的地区效应？ 轻链基因座对自身抗体也有影响吗 制作？ 2.I-E版本I-A认可在 自身免疫性移植物抗宿主反应？ A.在I-A和I-E认知上是否存在数量上的差异？ B.ANA在特异性上是否存在差异 I-E与I-A的差距？ C.肾小球肾炎在I-A-和I-A-之间有区别吗 I-E介导的GVH病？ D.GVH疾病是如何被下调的？ 这些拟议的研究将进一步从机制上理解 自身免疫学的遗传学。这样的知识将有助于揭示基本的 免疫调节功能障碍，产生全身自身免疫，并将 最终允许理性疗法的发展。