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