SJOGRENS XEROSTOMIA--VIRAL/IMMUNOLOGICAL ETIOLOGY

干燥口干症——病毒/免疫学病因

• 批准号: 2377649
• 负责人: William R. Gallaher
• 金额: $ 28.55万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-03-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2377649
• 关键词: CD antigens; SDS polyacrylamide gel electrophoresis; Sjogren's syndrome; T cell receptor; autoantibody; autoimmunity; autoradiography; biopsy; electron microscopy; flow cytometry; gag protein; gene expression; human immunodeficiency virus; human subject; immunocytochemistry; immunoprecipitation; laboratory mouse; lymphocyte; molecular cloning; nucleic acid sequence; pathologic process; plasmids; polymerase chain reaction; protein structure; virus antigen; virus protein; xerostomias

Preliminary studies have provided evidence for a possible retroviral etiology in Sjogren's Syndrome (SS; autoimmune exocrinopathy). The sera of a significant number of primary SS patients contained antibodies reactive with the major capsid protein of HIV, p24 (CA). In some cases reactivity to another gag protein p17 (MA) was also observed. A human intracisternal A-type particle (HIAP) was isolated from lymphoblastoid cells exposed to SS patient biopsy material. This retroviral particle is distinguishable from HIV by morphological and physical criteria, cellular distribution, and reverse transcriptase divalent cation preference. The overall goal of the proposed study is to genetically and immunochemically define the protein composition of this novel human retroviral particle, and its relationship to mechanisms of xerostomia in SS. The first specific aim this proposal is to detect and identify via polymerase chain reaction (PCR) the presence of HIAP cross-reactive with HIV p24. The second specific aim is to clone and express the probable (gag), protease (pro) and polymerase (pol) genes, and subclone the genes into plasmid systems permitting analysis of their products. The third aim is to model the cross-reactive, and additional, epitopes on these protein products, and otherwise, by expression in diverse systems, characterize the similarities and differences of these protein products, and otherwise, by expression in diverse systems, characterize the similarities and differences of these proteins with those of other known retroviruses. The fourth aim is to determine the reactivity of viral particles or cloned and expressed proteins, or derived peptides, with either antibodies or with appropriate "sensitized" lymphocytes derived from patients or immunized animals, including use of monoclonal antibodies. We will also determine the reactivity of antibodies with human salivary or other exocrine tissues, and the relationship of such reactivities to those naturally occurring in SS. Finally, we will determine by PCR the frequency of HIAP in archival lip biopsies preserved over a 20 year period and in samples from current SS patients, and relevant autoantibodies in a series of SS patients, with relevant controls derived from non-SS cases, each in the same series. The proposed studies will provide basic information regarding a heretofore undescribed human retroviral particle that has a possible, although yet to be established, role in SS xerostomia and other types of autoimmunity.

初步研究为可能的逆转录病毒提供了证据 Sjogren综合征（SS;自身免疫性外分泌病）的病因。 血清 大量的原发性SS患者含有抗体 用HIV的主要衣壳蛋白P24（CA）反应。 在某些情况下 还观察到对另一个GAG蛋白p17（MA）的反应性。 人类 从淋巴母细胞中分离出肠内A型颗粒（HIAP） 暴露于SS患者活检材料的细胞。 这个逆转录病毒颗粒 可以通过形态和身体标准与HIV区分开， 细胞分布和逆转录酶二价阳离子 偏爱。 拟议研究的总体目标是遗传和 免疫化学定义这种新型人的蛋白质组成 逆转录病毒粒子及其与静脉菌群机制的关系 SS。 该建议的第一个具体目的是通过 聚合酶链反应（PCR）HIAP交叉反应与 HIV P24。 第二个特定目的是克隆并表达可能 （GAG），蛋白酶（Pro）和聚合酶（POL）基因，并亚克隆基因 进入允许对其产品分析的质粒系统。 第三 目的是建模在这些上的交叉反应和其他表位 蛋白质产物，以及其他方式通过在不同系统中的表达 表征这些蛋白质产物的相似性和差异， 否则，通过在不同系统中的表达来表征 这些蛋白质与其他已知的蛋白质的相似性和差异 逆转录病毒。 第四个目的是确定病毒的反应性 颗粒或克隆和表达的蛋白质或衍生肽，具有 抗体或具有适当的“敏化”淋巴细胞 来自患者或免疫动物，包括使用单克隆 抗体。 我们还将确定抗体与 人类唾液或其他外分泌组织，以及这种关系 SS中天然发生的人的重新有效性。 最后，我们会的 通过PCR确定保留的档案唇活检中HIAP的频率 在20年的时间内以及目前的SS患者的样本中， 一系列SS患者的相关自身抗体，相关 来自非SS情况的对照，每个案例都在同一系列中。 这 拟议的研究将提供有关迄今为止的基本信息 未描述的人类逆转录病毒颗粒，尽管 要建立，在SS静脉菌群和其他类型的自身免疫中的作用。