Gene Expression and Diagnosis of Autoimmune Disease

描述（由申请人提供）：自身免疫性疾病被认为是由先天性或适应性免疫反应异常引起的，很可能具有遗传和环境因素。自身免疫性疾病的诊断通常很困难，因为症状可能相对非特异性。此外，没有可用的血液测试可以准确地排除具有这种症状的受试者中自身免疫性疾病的可能性。最好的情况是，需要一组测试和专家医生在一段时间内进行评估，以确定患者确实患有自身免疫性疾病。初步研究表明，外周血样品中基因表达的测量以高度的准确度将患有自身免疫性疾病的受试者与健康对照分开。在II期的第一部分，这些观察结果被扩展，以证明通过定量实时PCR测量的少于6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，可以实现具有高度的准确性。其他研究结果表明，这种方法在诊断类风湿性关节炎和系统性红斑狼疮患者的效用。现在建议扩展和扩大这些结果，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。为了更好地定义MS、RA和SLE的最佳诊断测试，我们将确定其他神经系统疾病、其他风湿性疾病或其他慢性疾病受试者的测试性能。 具体目标二。我们将在来自不同地理区域的个体队列中，在患有早期或不完全疾病的个体中，在患有MS、RA或SLE的个体的一级未受影响的亲属中，以及在开始每种疾病的标准治疗之前和之后的受试者中评估测试性能。 具体目标三。我们将设计测试标准，并根据FDA批准的要求对我们的测试进行验证研究。 我们预计，这些研究的结果将成为市场上的自身免疫诊断测试，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。与许多其他慢性疾病不同，这些疾病可以折磨儿童和年轻人，并对健康造成长期影响。更准确的血液检测将有助于疾病早期诊断，这是及时制定预防不可逆器官损伤的确定性治疗方法的关键。

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.