Antibodies to Ro ribonucleoproteins as biomarkers in Sjogren's syndrome

Ro 核糖核蛋白抗体作为干燥综合征的生物标志物

基本信息

批准号：
7268121
负责人：
Sandra L. Wolin
金额：
$ 22.84万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2009-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7268121
关键词：
Antibodies Autoantibodies Autoimmune Diseases Autoimmunity Biological Markers Cardiac Cells Clinical Cutaneous Lupus Erythematosus Cysteine Diagnosis Disease Disease Progression Drug or chemical Tissue Distribution Epithelial Cells Etiology Exocrine Glands Fibroblasts Goals Human Immune response Immunoblotting Individual Infiltration Location Lupus Lupus Erythematosus, Cutaneous, Subacute Lymphocyte Macromolecular Complexes Modification Morbidity - disease rate Mus Neonatal lupus erythematosus Outcome Oxidative Stress Pathogenesis Patients Play Proteins Rheumatism Ribonucleoproteins Role SS-A antibodies SS-A antigen Salivary Serum Sjogren&apos s Syndrome Syndrome Systemic Lupus Erythematosus Tissues Xerostomia cell type eye dryness insight intracellular protein transport keratinocyte novel particle protein localization location research study response

项目摘要

DESCRIPTION (provided by applicant): Sjogren's syndrome is a common autoimmune disease characterized by focal lymphocytic infiltration of exocrine glands. Although Sjogren's syndrome is associated with significant morbidity, the etiology is unknown, and diagnosis is difficult. To date, the most useful biomarker for Sjogren's syndrome is the presence of anti-Ro and anti-La autoantibodies. These antibodies are directed against ribonucleoprotein particles (RNPs) consisting of the Ro60 protein, the La protein, and nocoding RNAs called Y RNAs. However, while antibodies to Ro60 and/or La occur in 38-90% of Sjogren's syndrome patients, these antibodies also occur in patients with other rheumatic diseases, including systemic lupus erythematosus. The objective of this exploratory project is to identify novel biomarkers that will expedite correct diagnosis of Sjogren's syndrome and yield insights into etiology and/or disease progression. Our specific approach is to focus on newly identified components of the Ro60 RNPs and on oxidatively modified forms of Ro60. Our first aim is to determine whether any of nine novel Ro-associated proteins are specific targets of the immune response in Sjogren's syndrome. Our second aim is to examine the tissue distribution and subcellular localization of these proteins. The finding that a targeted protein is most abundant in salivary epithelial cells, while other proteins are more abundant in keratinocytes, may give insights into why some patients with anti-Ro60 antibodies develop Sjogren's syndrome, while others develop distinct rheumatic diseases. Our third aim is to determine if anti-Ro60 autoantibodies are preferentially directed against oxidatively modified forms of the protein. The finding that patients target oxidized forms of Ro60 may be helpful for differentiating the various syndromes associated with these antibodies, may be useful for predicting clinical outcomes, and may yield insights into the mechanisms by which autoimmunity in Sjogren's syndrome originates. Lay summary: Sjogren's syndrome, a disease characterized by dry eyes and dry mouth, is often confused with other illnesses. Our goal is to identify whether Sjogren's syndrome patients produce autoantibodies that will be useful for diagnosis and for predicting the course of the disease in individual patients.

描述（由申请人提供）：Sjogren综合征是一种常见的自身免疫性疾病，其特征是外分泌腺的局灶性淋巴细胞浸润。尽管Sjogren综合征与明显的发病率有关，但病因尚不清楚，诊断很困难。迄今为止，Sjogren综合征最有用的生物标志物是抗RO和抗LA自身抗体的存在。这些抗体针对由Ro60蛋白，LA蛋白和称为Y RNA的Nocododing RNA组成的核糖核蛋白颗粒（RNP）。但是，尽管Sjogren综合征患者的38-90％发生了RO60和/或LA的抗体，但这些抗体也发生在其他风湿病患者（包括全身性狼疮性红斑狼疮）的患者中。该探索性项目的目的是确定新型的生物标志物，可以加快对Sjogren综合征的正确诊断并产生对病因和/或疾病进展的见解。我们的特定方法是专注于RO60 RNP的新鉴定的组件以及RO60的氧化修饰形式。我们的第一个目的是确定九种新型的RO相关蛋白中的任何一种是Sjogren综合征中免疫反应的特定靶标。我们的第二个目的是检查这些蛋白质的组织分布和亚细胞定位。在唾液上皮细胞中，靶向蛋白最丰富的发现，而其他蛋白质在角质形成细胞中更丰富，可以深入了解为什么有些抗Ro60抗体患者会产生sjogren综合征，而另一些患者会产生独特的流变疾病。我们的第三个目的是确定抗Ro60自身抗体是否优先针对蛋白质的氧化修饰形式。患者靶向RO60的患者的发现可能有助于区分与这些抗体相关的各种综合征，可能有助于预测临床结局，并且可能对Sjogren综合征自身免疫性的机制产生见解。 Lay摘要：Sjogren综合征是一种以干眼和口干为特征的疾病，通常与其他疾病混淆。我们的目标是确定Sjogren综合征患者是否产生自身抗体，这些自身抗体对于诊断和预测个别患者的疾病进程。