EXPERIMENTAL INDUCTION OF SLE BY ALTERED IA

通过改变 IA 实验诱导 SLE

• 批准号: 3156750
• 负责人: ROBERT A. EISENBERG
• 金额: $ 16.58万
• 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/3156750
• 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.

当前的申请提议调查遗传 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。 它将集中于两个基因 在一般免疫中起主要作用的位点：免疫球蛋白和 主要组织相容性复合体。 拟议的工作基于以前的 观察到这些位点的某些等位基因赋予特定的 对自身免疫的易感性。 具体目标概述为 如下： 1. Igh(b) 同种异型如何有利于自身抗体的产生？ 一个。 b 同种异型效应是否会扩展到其他同种型？ 自身抗体的特异性？ b. b 同种异型偏斜是否针对自身抗体？ c. 自身抗体的 b 同种异型倾斜是否发生在其他菌株中 组合？ d. 同种异型效应是由V区还是C区引起的？ e. b同种异型的体细胞突变是否比a更大 异型？ f. 是否存在恒定区域效应？ g。 轻链位点对自身抗体也有影响吗 生产？ 2. I-E版本I-A识别在系统中的相对作用是什么？ 自身免疫移植物抗宿主反应（GVH）？ 一个。 I-A 与 I-E 识别是否存在数量差异？ b. ANA 的精细特异性是否存在差异？ I-E 与 I-A 的差异？ c. I-A- 和 I-A- 之间的肾小球肾炎有差异吗？ I-E介导的GVH疾病？ d. GVH 疾病如何下调？ 这些拟议的研究将进一步加深对机制的理解 自身免疫的遗传学。 这些知识将有助于揭示基本的 免疫调节功能障碍会产生全身性自身免疫，并会 最终允许合理治疗的发展。