Gene Expression and Diagnosis of Autoimmune Disease

描述(申请人提供)：自身免疫性疾病被认为是由先天或适应性免疫反应异常引起的，很可能有遗传和环境因素。自身免疫性疾病的诊断通常很困难，因为症状可能相对没有特异性。此外，任何可用的血液测试都不能准确地排除具有这种症状的受试者患自身免疫性疾病的可能性。充其量，需要一位专家医生在一段时间内进行一系列测试和评估，才能确定患者确实患有自身免疫性疾病。初步研究表明，外周血样本中基因表达的测量可以高度准确地将自身免疫性疾病患者与健康对照区分开来。在第二阶段的第一部分，这些观察被扩展到证明通过定量实时PCR测量的少于六个基因的表达水平可以产生类似的结果。结果表明，MS患者与正常对照的分离具有较高的准确度。其他发现表明，这种方法在类风湿性关节炎和系统性红斑狼疮患者的诊断中是有效的。现在建议扩大和扩大这些结果，以包括更大和更多样化的患者群体，并评估纵向变化。提出了三个具体目标： 具体目标一.为了更好地确定MS、RA和SLE的最佳诊断测试，我们将确定患有其他神经学、其他风湿病或其他慢性病的受试者的测试表现。 具体目标II.我们将评估来自不同地理区域的人群、早期或不完全疾病患者、MS、RA或SLE患者的一级未受影响亲属以及每种疾病的标准治疗开始前后的受试者的测试表现。 具体目标III。我们将根据FDA批准的要求设计测试标准并进行验证研究。 我们预计，这些研究的结果将被推向市场，用于自身免疫诊断，这将对患者护理产生重大影响。 公共卫生相关性：自身免疫性疾病影响5%的人口。与许多其他慢性病不同，这些疾病会折磨儿童和年轻人，带来长期的健康后果。获得更准确的血液测试将有助于疾病早期阶段的诊断，这是及时制定明确治疗以防止不可逆转的器官损害的关键。

DESCRIPTION (provided by applicant): Autoimmune diseases are thought to arise from abnormalities in innate or adaptive immune responses and most likely have both genetic and environmental components. Diagnosis of autoimmune disease is often difficult, as the symptoms can be relatively nonspecific. Furthermore, no available blood test can accurately exclude the possibility of an autoimmune disease in a subject with such symptoms. At best, a battery of tests and evaluation by a specialist physician over a period of time are required to establish that a patient does in fact have an autoimmune disorder. Initial studies have demonstrated that measurement of gene expression in peripheral blood samples separates subjects with autoimmune disorders from healthy controls with a high degree of accuracy. In the first part of the Phase II period, these observations were extended to demonstrate that expression levels of a less than six genes measured by quantitative real-time PCR can produce similar results. The results show that separation of MS patients from normal controls can be achieved with a high degree of accuracy. Other findings indicate utility of this approach in the diagnosis of patients with rheumatoid arthritis and systemic lupus erythematosus. It is now proposed to extend and expand these results to include larger and more diverse patient groups and to evaluate longitudinal changes. Three specific aims are proposed: Specific Aim I. To better define optimum diagnostic tests for MS, RA, and SLE, we will determine test performance in subjects with other neurologic, other rheumatologic conditions or other chronic diseases. Specific Aim II. We will evaluate test performance in cohorts of individuals from different geographic regions, in individuals with early or incomplete disease, in first-degree unaffected relatives of individuals with MS, RA, or SLE, and in subjects prior to and after initiation of standard therapies for each disease. Specific Aim III. We will design test standards and perform validation studies for our tests as required for FDA approval. We anticipate that the result of these studies will be marketed tests for autoimmune diagnosis that will have a significant impact on patient care. PUBLIC HEALTH RELEVANCE: Autoimmune diseases affect 5% of the population. Unlike many other chronic diseases, these maladies can afflict children and young adults, with long-term health consequences. Diagnosis in early disease stages would be facilitated by the availability of more accurate blood tests, and this is key to timely institution of definitive therapies for prevention of irreversible organ damage.