A Sjogrens Syndrome Diagnostic

描述(申请人提供)：SJ“格伦综合征(SS)是一种自体炎症状态，以一系列症状为特征，包括眼睛和嘴巴干燥。尽管这种情况相对常见，在美国有多达400万人受到影响，但准确的诊断一直很复杂，而且基本上无效。如果不进行诊断，因此不进行治疗，SS可能会发展为显著的发病率，并将患某些形式癌症的风险增加100倍。因此，SS患者的识别是一项迫切的未得到满足的需求。目前的SS诊断工具有限，部分原因是症状范围广泛，并经常与其他自体炎症性疾病重叠。在这项研究中，我们将使用全血RNA的全基因组表达谱结合多变量分析来识别SS疾病的诊断生物标记物。我们的初步数据支持这样的假设，即这些生物标志物可以被识别出来，正确地对患者进行分类，并为目前的SS诊断方法提供强有力的辅助手段。方法我们的初步数据表明，与目前的诊断实验室测试相比，基于多变量基因表达的算法在区分SS、类风湿关节炎(RA)和未受影响的对照组方面具有更好的性能。在这项建议中，将开发一个原型多变量算法，利用系统性红斑狼疮(SLE)作为标准SS区分的附加条件。此外，我们将只包括没有SS重叠的RA和SLE患者，以便在未来的队列中有可能进行二次SS诊断。 公共卫生相关性：在这项应用中，我们建议创建一种诊断原发性干燥综合征(PSS)的简单血液测试。由于症状可能是微妙的、多种多样的，并且经常被其他自体炎症条件所掩盖，目前诊断这种常见疾病的技术已经无效。我们建议创建一种诊断测试，通过包括可能与PSS同时发生的常见自身免疫性疾病来考虑这些微妙之处，从而比目前可能的情况更有效地识别PSS。

DESCRIPTION (provided by applicant): Sj"gren's Syndrome (SS) is autoinflammatory condition, characterized by a plethora of symptoms, including dry eyes and mouth. Despite the fact that the condition is relatively common, with up to 4 million persons affected in the US, accurate diagnosis has been complex and largely ineffective. Left undiagnosed, and thus untreated, SS can progress to significant morbidity and increase the risk of certain forms of cancer up to 100 fold. The identification of SS patients is, therefore, a pressing unmet need. Current SS diagnostic tools have been limited, in part because of the wide range of symptoms and frequent overlap with other autoinflammatory disorders. In this study, we will use genome-wide expression profiling of whole blood RNA coupled with multivariate analysis to identify SS diagnostic biomarkers of disease. Our preliminary data support the hypothesis that such biomarkers can be identified that correctly classify patients and provide a powerful adjunct to current SS diagnostic methods. Methods Our preliminary data demonstrate that a multivariate gene expression-based algorithm has superior performance to distinguish among SS, rheumatoid arthritis (RA), and unaffected controls than current diagnostic laboratory tests. In this proposal, a prototype multivariate algorithm will be developed utilizing systemic lupus erythematosus (SLE) as an additional condition within a standard SS differential. Moreover, we will only include RA and SLE patients without SS overlap to allow the potential for secondary SS diagnosis in future cohorts. PUBLIC HEALTH RELEVANCE: In this application we propose to create a simple blood test for the diagnosis of primary Sj"gren's Syndrome (pSS). Due to the fact that symptomologies can be subtle, varied and often masked by other auto inflammatory conditions, current technologies for diagnosis of this common condition have been ineffective. We propose to create a diagnostic test that takes these subtleties into account by including common autoimmune diseases that can occur simultaneously with pSS thereby, identifying pSS more effectively than currently possible.