NOVEL PROTEINS ASSOCIATED WITH SS-A/RO IN TARGET ORGANS

描述：（改编自申请人摘要）-自身抗体反应性 SS-A/Ro抗原是SLE的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狼疮 红斑狼疮（NLE）。两种细胞蛋白，60和52 kDa，已被确定， 作为自身免疫反应的主要目标。远景目标 目前的建议是了解这一具体的起源 同源抗原的自身反应性和细胞功能。等 知识应该提供关键的见解的发病机制， 相关疾病，可能不同的每一个临床表型。最近一 一种新的75 kDa磷蛋白（pp 75）被鉴定为相互作用伴侣 60 kDa的SS-A/Ro蛋白。此外，它已被确定为一个 干燥综合征患者血清中抗体识别的自身抗原 综合征和NLE儿童的母亲。因此，三个具体目标是 旨在检查SS-A/Ro自身抗体在 四种疾病实体，并评估是否有任何候选蛋白质伴侣， SS-A/Ro可能为自身免疫发病机制提供新的线索。目标1将重点 进一步明确了pp 75与60 kDa的关系 SS-A/Ro.其他实验将检查pp 75是否与 额外的蛋白质。目的2探讨SS-A/Ro抗原的相关性 与皮肤中其他组织特异性和普遍表达的蛋白质一起， 使用酵母双杂交筛选各自cDNA 图书馆.基本原理是每个靶器官可能具有独特的 可与SS-A/Ro蛋白相互作用的蛋白质。差异和 在三个受影响的器官中定义的相互作用之间的相似性应该是 信息量很大目标3将解决抗pp 75抗体的流行， 其他假定的组织特异性候选相互作用配偶体的抗体， 四种疾病的血清。临床相关性将加强 抗体与组织损伤发病机制的关系。的 希望拟议的研究将大大推动我们目前的研究， 了解SS-A/Ro抗原/抗体系统及其在 针对特定器官的疾病状态。

DESCRIPTION: (Adapted from the applicant's abstract) - Autoantibody reactivity with the SS-A/Ro antigen is an important clinical serological marker for SLE, Sjogren's syndrome, sub acute cutaneous lupus erythematosus, and neonatal lupus erythematosus (NLE). Two cellular proteins, 60 and 52 kDa, 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 60kDa SS-A/Ro 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-A/Ro autoantibodies in the four disease entities and to evaluate if any candidate protein partner(s) of SS-A/Ro may provide new clues to the autoimmune pathogenesis. Aim 1 will focus on the identification of pp75 and further define its relationship with 60kDa SS-A/Ro. Additional experiments will examine whether pp75 is associated with additional proteins. Aim 2 will explore the association of SS-A/Ro 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 that 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, it is hoped, will significantly advance our current understanding of the SS-A/Ro antigen/antibody system and its functional role in disease states that target specific organs.