Novel Proteins Associated with SS-A/Ro in Target Organs

靶器官中与 SS-A/Ro 相关的新型蛋白质

• 批准号: 6708357
• 负责人: EDWARD K CHAN
• 金额: $ 25.43万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6708357
• 关键词: Sjogren' s syndrome; antigen antibody reaction; autoantibody; autoantigens; autoimmune disorder; biomarker; clinical research; genetic library; human tissue; immunopathology; protein protein interaction; ribonucleoproteins; systemic lupus erythematosus; yeast two hybrid system

DESCRIPTION: (Verbatim) Autoantibody reactivity with the SS-AIRo antigen is an important clinical serological marker for SLE, Sjogren's syndrome, subacute cutaneous lupus erythematosus and neonatal lupus erythematosus (NLE). Two cellular proteins, 60 and 52kDa, have been identified as the predominant targets of the autoimmune response. The long-term objectives of the current proposal are to understand both the origin of this specific autoreactivity and the cellular function of the cognate antigens. Such knowledge should provide critical insights into the pathogenesis of the associated diseases that may differ for each clinical phenotype. Recently a novel 75kDa phosphoprotein (pp75) has been identified as an interaction partner for the 6OkDa SS-AIRo protein. In addition it has been identified as an autoantigen recognized by antibodies in sera from patients with Sjogren's syndrome and mothers of children with NLE. Accordingly, three Specific Aims are designed to examine the overall significance of SS-AIRo autoantibodies in the four disease entities and to evaluate if any candidate protein partner(s) of SS-AIRo may provide new clues to the autoimmune pathogenesis. Aim 1 will focus on the identification of pp75 and further define its relationship with 6OkDa SS-A/Ro. Additional experiments will examine whether pp75 is associated with additional proteins. Aim 2 will explore the association of SS-AJRo antigens with other tissue-specific and ubiquitously expressed proteins in the skin, heart, and salivary glands using yeast two-hybrid screen with respective cDNA libraries. The rationale is that each of the target organs may have unique proteins which are available to interact with SS-A/Ro proteins. Differences and similarities among interactions defined in the three affected organs should be highly informative. Aim 3 will address the prevalence of anti-pp75 and antibodies to other putative tissue-specific candidate interaction partners in sera from the four disease groups. Clinical correlations will strengthen the relationship of the antibodies to the pathogenesis of tissue injury. The proposed studies will significantly advance our current understanding of the SS-AIRo antigen/antibody system and its functional role in disease states which target specific organs.

描述：（逐字）自身抗体反应性与SS-AIRO抗原是一种 SLE，Sjogren综合征，亚急性的重要临床血清学标记 皮肤红斑狼疮和新生儿狼疮红膜（NLE）。二 细胞蛋白（60和52KDA）已被确定为主要 自身免疫反应的目标。当前的长期目标 建议既要了解这种特定自动反应性的起源，又要了解 同源抗原的细胞功能。这样的知识应提供 对可能的疾病的发病机理的批判性见解 每个临床表型都不同。最近一种新型的75KDA磷蛋白 （PP75）已被确定为6OKDA SS-AIRO的交互合作伙伴 蛋白质。另外，它已被确定为由 Sjogren综合征患者血清中的抗体和母亲 NLE的孩子。因此，设计了三个特定目标来检查 SS-AIRO自动抗体在四个疾病实体中的总体意义 评估SS-AIRO的任何候选蛋白伴侣是否可以提供新的 自身免疫发病机理的线索。 AIM 1将专注于识别 PP75并进一步定义了其与6OKDA SS-A/RO的关系。额外的 实验将检查PP75是否与其他蛋白质相关。 AIM 2将探索SS-Ajro抗原与其他的关联 组织特异性和普遍表达的皮肤，心脏和 使用酵母双杂交筛网和各自的cDNA文库的唾液腺。 理由是每个目标器官可能具有独特的蛋白质 可与SS-A/RO蛋白相互作用。异同 在三个受影响器官中定义的互动中应高度高度 内容丰富。 AIM 3将解决抗PPP75和抗体的患病率 其他推定的组织特异性候选相互作用伙伴来自血清中的 四个疾病组。临床相关性将加强 组织损伤发病机理的抗体。拟议的研究将 显着提高我们目前对SS-AIRO抗原/抗体的理解 系统及其在针对特定器官的疾病状态中的功能作用。