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 亚急性干燥综合征SLE的重要临床血清学标志 皮肤红斑狼疮和新生儿红斑狼疮。二 60和52 kDa的细胞蛋白已被确定为主要的 自身免疫反应的靶标。当前的长期目标 建议既要理解这种特殊的自动反应的起源，又要理解 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关键见解可能 不同的临床表型不同。新近发现的一种新的75 kDa磷酸蛋白 (Pp75)已被确定为6OkDa SS-Airo的交互合作伙伴 蛋白。此外，它还被确认为一种被 干燥综合征患者及其母亲血清中抗体的检测 患有NLE的儿童。因此，设计了三个具体目标来审查 SS-AIRO自身抗体在四种疾病实体和 评估SS-AIRO的任何候选蛋白质合作伙伴(S)是否可以提供新的 自身免疫发病机制的线索。目标1将重点放在确定 Pp75，并进一步确定其与6OkDa SS-A/Ro的关系。其他内容 实验将检验pp75是否与额外的蛋白质有关。 目标2将探索SS-Ajro抗原与其他 组织特异性和普遍表达的蛋白质在皮肤、心脏和 用酵母双杂交技术筛选唾液腺组织中各自的cDNA文库。 其基本原理是，每个靶器官可能具有独特的蛋白质，这些蛋白质 可与SS-A/Ro蛋白相互作用。差异和相似之处 在三个受影响的器官中定义的相互作用应该是高度 见多识广。目标3将解决抗pp75抗体和抗体的流行问题 血清中其他可能的组织特异性候选相互作用伙伴 四个疾病组。临床相关性将加强与 该抗体对组织损伤的发病机制有影响。拟议的研究将 极大地提高了我们目前对SS-AIRO抗原/抗体的了解 系统及其在针对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.