权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

IMMUNOLOGY OF THE AUTOANTIGENS RO/SSA AND LA/SSB

自身抗原 RO/SSA 和 LA/SSB 的免疫学

基本信息

批准号：
3446022
负责人：
Courtney Montgomery
金额：
$ 5.04万
依托单位：
OKLAHOMA MEDICAL RESEARCH FOUNDATION
依托单位国家：
美国
项目类别：
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/3446022
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

项目摘要

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.

沉淀抗核糖核蛋白Ro/SSA和 LA/SSB常见于系统性红斑狼疮(SLE)和干燥综合征(SS)。这些沉淀的存在或不存在自身抗体与截然不同的临床表现密切相关。和疾病亚组。例如，两种疾病的系统性表现干燥综合征和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的工作导致了它们的提纯和它们的进一步分子表征及敏感材料的研究进展检测他们各自的自身抗体。对这些化验方法的研究已经不仅使我们更好地理解了人类的疾病过程，而且它们在动物身上具有免疫原性的证明也是如此。这个项目将测试体液自身免疫反应的假设对Ro/SSA和La/SSb在SLE和SS中的作用受到限制。这将是确定的 Ro/SSA和La/SSb的全部或仅部分表位与相关的SLE和SS自身抗体。这件事将首先完成抗Ro/SSA和抗La/SSB血清及单抗的研制与应用抗体的来源有很多。它们抑制系统性红斑狼疮和 SS抗Ro/SSA和抗La/SSB反应性(反之亦然) 下定决心。抗Ro/SSA和抗La/SSB试剂的来源包括兔、小鼠异种免疫抗血清及小鼠单抗抗体，来自SLE和SS患者的血清，正常人抗Ro/SSA和抗La/SSB，人骨髓瘤单抗和血清来自C2缺乏和抗-Ro/SSA的患者(及其家属)。这个这些试剂的每一种来源的表征将在将允许解决B之外的其他重要问题的方式细胞自身免疫谱限制。抗Ro/SSA抗体的应用研究抗独特型6-49也将用抗Ro/SSA固相进行阴性患者和正常献血员检测阳性、抗Ro/SSA沉淀确定该独特型标记与抗Ro/SSA抗体的相关性对B细胞谱系限制的可能解释。建议数生物化学和免疫化学方法纯化RNA-蛋白质阶段免疫吸附试验、免疫、杂交瘤融合、克隆、展开和分析都是校长的标准用法调查员的实验室。