IMMUNOLOGY OF THE AUTOANTIGENS RO/SSA AND LA/SSB

自身抗原 RO/SSA 和 LA/SSB 的免疫学

• 批准号: 3446292
• 负责人: Courtney Montgomery
• 金额: $ 5.33万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3446292
• 关键词: B lymphocyte; Sjogren's syndrome; arthritis; autoantibody; autoantigens; autoimmune disorder; congenital heart disorder; heart block; humoral immunity; hybridomas; immunochemistry; monoclonal antibody; multiple myeloma; reagent /indicator; systemic lupus erythematosus

Precipitating autoantibodies against the ribonucleoproteins Ro/SSA and La/SSB are commonly encountered in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). The presence or absence of these precipitating autoantibodies is strongly associated with very different clinical findings and disease subsets. For example, both the systemic manifestations of Sjogren's syndrome as well as most cases of congenital complete heart block are very closely associated with anti-Ro/SSA precipitating antibodies. Our recent work with Ro/SSA and La/SSB has led to their purification and their further molecular characterization and the development of sensitive assays for their respective autoantibodies. Studies with these assays have not only led to better understanding of the human disease processes but also to the demonstration that they are immunogenic in animals. This project will test the hypothesis that the humoral autoimmune responses to Ro/SSA and La/SSB in SLE and SS are restricted. It will be determined whether all or only some of the epitopes of Ro/SSA and La/SSB react with the relevant SLE and SS autoantibodies. This will be done by first developing and applying anti-Ro/SSA and anti-La/SSB sera and monoclonal antibodies from a number of sources. Their capacity to inhibit the SLE and SS anti-Ro/SSA and anti-La/SSB reactivity (and vice versa) will then be determined. Sources of anti-Ro/SSA and anti-La/SSB reagents will include heteroimmune antisera from rabbits and mice and murine monoclonal antibodies, sera from SLE and SS patients, normal individuals with anti-Ro/SSA and anti-La/SSB, human myeloma monoclonal antibodies, and sera from patients (and family members) with C2 deficiency and anti-Ro/SSA. The characterization of each of these sources of reagents will be done in a manner that will permit addressing additional important questions beyond B cell autoimmune repertoire restriction. A study using the anti-Ro/SSA anti-idiotype 6-49 will also be performed with anti-Ro/SSA solid phase assay positive, anti-Ro/SSA precipitin negative patients and normal donors to determine the correlation of this idiotypic marker with anti-Ro/SSA as a potential explanation for B cell repertoire restriction. The proposed biochemical and immunochemical methods of RNA-protein purification, solid phase immunosorbent assays, immunization, hybridoma fusions, cloning, expansion and analysis are all in standard use by the principal investigator's laboratory.

针对核糖核蛋白Ro/SSA和 La/SSB常见于系统性红斑狼疮（SLE）， 干燥综合征（SS）。 这些沉淀的存在或缺乏 自身抗体与非常不同的临床表现密切相关 和疾病亚群。 例如，无论是系统性的表现， 干燥综合征以及大多数先天性完全性心脏传导阻滞 与抗Ro/SSA沉淀抗体密切相关。 我们最近对Ro/SSA和La/SSB的研究已经导致了它们的纯化， 它们的进一步分子表征和灵敏的 测定其各自的自身抗体。 使用这些检测方法进行的研究 不仅让我们更好地了解人类疾病的过程， 也证明了它们在动物中具有免疫原性。 这个项目将检验体液自身免疫反应 在SLE和SS中，Ro/SSA和La/SSB是受限制的。 将确定 Ro/SSA和La/SSB的所有或仅一些表位与 相关SLE和SS自身抗体。 这将首先完成 抗Ro/SSA和抗La/SSB血清及单克隆抗体的研制和应用 抗体来自不同的来源。 它们抑制SLE的能力， SS抗Ro/SSA和抗La/SSB反应性（反之亦然）， 测定 抗Ro/SSA和抗La/SSB试剂的来源包括 兔和小鼠异源免疫抗血清及鼠单克隆抗体 抗体，来自SLE和SS患者的血清，正常个体， 抗Ro/SSA和抗La/SSB、人骨髓瘤单克隆抗体和血清 来自C2缺乏和抗Ro/SSA的患者（和家庭成员）。 的 这些试剂来源中的每一种的表征将在 能够解决B以外的其他重要问题的方式 细胞自身免疫谱限制。 使用抗Ro/SSA的研究 还将使用抗Ro/SSA固相进行抗独特型6-49 检测阳性、抗Ro/SSA沉淀素阴性患者和正常供体 为了确定这种独特型标记与抗Ro/SSA的相关性， B细胞库限制的潜在解释。 拟议 RNA-蛋白质纯化的生物化学和免疫化学方法，固体 阶段免疫吸附测定，免疫，杂交瘤融合，克隆， 扩展和分析都是校长的标准用法， 调查员的实验室。