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，通常需要一系列测试和一段时间的观察才能确定患者确实患有自身免疫性疾病。利用微阵列技术，我们发现，患有四种不同自身免疫性疾病中的任何一种的人都有一个共同的基因表达特征，该特征独立于特定的临床实体，但与正常的免疫反应完全不同。基于这些观察，我们开发了一种简单的测试，用于排除受试者患有自身免疫性疾病的可能性。在第一阶段，我们已经证明了这种测试存在于早期疾病中，并与非自身免疫性疾病有明显的区别。我们已经确认了我们阵列中的基因的身份，并开发了一种生产诊断阵列的方法。这项第二阶段的建议是继续这项工作，有三个具体目标。一是优化基因阵列平台。第二个是测试早期未分化疾病患者和其他疾病患者的诊断工具，以确认特异性。第三是将结果与现有的测试结果进行比较。这一阶段的结果将是一项在研究和临床护理中应用可行的测试

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 a period of observation are usually required to establish that a patient does in fact have an autoimmune disorder. Using microarray technology, we have found that individuals with any of four distinct autoimmune diseases have a common gene expression signature that is independent of the specific clinical entity, but which is totally distinct from the normal immune response. Based upon these observations, we have developed a simple test for excluding the possibility that a subject has an autoimmune disorder. In Phase I we have shown that this test is present in early disease and has distinct differences from non-autoimmune disorders. We have confirmed the identities of the genes in our arrays and developed an approach for production of diagnostic arrays. This Phase II proposal is to continue this work has three specific aims. The first is to optimize the gene array platform. The second is to test the diagnostic tool in patients with early, undifferentiated disease and with other diseases to confirm specificity. The third is to compare the results to those obtained with existing tests. The result of this phase will be a test that is feasible for applications in research and clinical care