Gene Expression and Diagnosis of Diabetes

描述（由申请人提供）：自身免疫性疾病很难诊断，因为其症状可能是其他疾病的典型症状，而且相当模糊。目前还没有可用的血液检测能够准确地排除或包括受试者自身免疫性疾病的可能性，通常需要一系列的检测和一段时间的观察。一个单一的测试可以很容易地区分自身免疫性和非自身免疫性疾病，这将使医生集中精力在影响患者的特定疾病上。这对糖尿病至关重要，因为1型糖尿病和2型糖尿病的治疗方法完全不同。利用微阵列技术，我们比较了四种不同自身免疫性疾病个体、免疫前后正常对照个体和其他慢性疾病个体外周血单个核细胞基因表达的差异。我们发现每个自身免疫性疾病患者都有一个共同的基因表达特征，它独立于特定的自身免疫性疾病，但与正常的免疫反应完全不同，并且在其他慢性疾病患者中没有观察到。基于这些数据，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。这种测试的主要优点是它比现有的测试更快、更准确。该测试迄今已100%准确地将自身免疫性患者与其他患者区分开来。现在我们要把注意力转向糖尿病。本提案的第一个目标是收集I型和II型糖尿病患者的基因表达数据，以设计具有最佳预测能力的测试。第二个目标是通过检查患有高血糖但尚未明确诊断为任何一种糖尿病的个体来验证该测试。长期目标是利用微阵列实验的结果来开发对自身免疫性和非自身免疫性疾病患者的治疗管理具有预测价值的测试。

DESCRIPTION (provided by applicant): Autoimmune diseases are difficult to diagnose, as the symptoms can be typical of other conditions and quite vague. No currently available blood test accurately excludes or includes the possibility of an autoimmune disease in a subject, and a battery of tests and a period of observation are usually required. A single test that could readily distinguish between an autoimmune and non-autoimmune disorder would allow physicians to focus efforts on the specific disease that affects the patient. This is critical for diabetes since the treatments for type I and type II diabetics are completely different. Using microarray technology, we have compared differences in gene expression in peripheral blood mononuclear cells among individuals with four distinct autoimmune diseases, normal control individuals before and after immunization, and individuals with other chronic diseases. We find that each individual with autoimmune disease has a common gene expression signature that is independent of the specific autoimmune disease but is totally distinct from the normal immune response and is not observed in individuals with other chronic diseases. Based on these data, we have developed a simple test for excluding the possibility that a subject has an autoimmune disorder. The main advantage of this test is that it is a quicker and more accurate test than those currently available. This test has thus far distinguished autoimmune patients from others with 100% accuracy. We now want to turn our attention to diabetes. The first goal of this proposal is to collect gene expression data from patients with type I and type II diabetes to design a test with optimal predictive power. The second goal is to validate the test by examining individuals who have hyperglycemia but do not yet carry a clear-cut diagnosis of either type of diabetes. Long-term goals are to use results from microarray experiments to develop tests that have predictive value for the therapeutic management of individuals with autoimmune and non-autoimmune diseases.