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是困难的，因为症状可能相对非特异性。此外，没有任何可用的血液测试可以准确地排除具有此类症状的受试者患有自身免疫性疾病的可能性。最好的情况是，通常需要一系列的测试和一段时间的观察来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的个体都有一个共同的基因表达特征，它独立于特定的临床实体，但与正常的免疫反应完全不同。基于这些观察结果，我们开发了一个简单的测试来排除受试者患有自身免疫性疾病的可能性。在I期，我们已经证明该测试存在于早期疾病中，并且与非自身免疫性疾病有明显区别。我们已经确认了我们的阵列基因的身份，并开发了一种生产诊断阵列的方法。第二阶段的建议是继续这项工作，它有三个具体目标。首先是优化基因阵列平台。二是在早期、未分化的疾病和其他疾病患者中测试诊断工具，以确认特异性。第三是将结果与现有测试结果进行比较。这一阶段的结果将是一项在研究和临床护理中应用的可行测试

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