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

描述：（逐字）自身抗体与SS-AIRo抗原的反应性是一种免疫反应。 SLE重要临床血清学标志物，干燥综合征，亚急性 皮肤红斑狼疮和新生儿红斑狼疮（NLE）。两 细胞蛋白，60和52 kDa，已被确定为主要的 自身免疫反应的靶点当前的长期目标 我们的建议是了解这种特异性自身反应性的起源， 同源抗原的细胞功能。这样的知识应该提供 对相关疾病的发病机制的重要见解， 不同的临床表现型。最近发现了一种新的75 kDa磷蛋白 （pp 75）已被确定为60 kDa SS-AIRo的相互作用伙伴 蛋白此外，它已被确定为一种自身抗原， Sjogren综合征患者和母亲血清中的抗体 儿童NLE因此，设计了三个具体目标，以审查 SS-AIRo自身抗体在四种疾病实体中的总体显著性， 评估SS-AIRo的任何候选蛋白质伴侣是否可以提供新的 自身免疫发病机制的线索目标1将侧重于确定 pp 75，并进一步确定了其与60 kDa SS-A/Ro的关系。额外 实验将检验pp 75是否与其它蛋白质相关。 目的2将探索SS-AJRo抗原与其他抗原的关联 组织特异性和普遍表达的蛋白质在皮肤，心脏， 唾液腺使用酵母双杂交筛选各自的cDNA文库。 基本原理是每个靶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 在三个受影响的器官中定义的相互作用之间， 信息量大。目标3将讨论抗pp 75抗体和 其他假定的组织特异性候选相互作用伴侣在血清中从 四种疾病。临床相关性将加强 组织损伤发病机制的抗体。拟议的研究将 显著推进了我们目前对SS-AIRo抗原/抗体的理解 系统及其在靶向特定器官的疾病状态中的功能作用。

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.