SBIR-STTR Award

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.

Thesaurus Terms:
autoimmune disorder, diabetes mellitus, diagnostic test, gene expression, technology /technique development diagnosis design /evaluation, hyperglycemia clinical research, human subject, microarray technology, questionnaire

Autoimmune diseases are difficult to diagnose, as the symptoms can be nonspecific. 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 mellitus (DM), which has two subsets, Type I and Type II. The subsets of DM differ in pathogenesis, treatment and prognosis. Using microarray technology, we have compared differences in gene expression in peripheral blood mononuclear cells among patients with autoimmunity, including type I DM, and patients with non-autoimmune Type II DM. In Phase I, we investigated differences in gene expression between the DM types in adults and children. The findings from these studies suggest that we can readily identify subgroups of patients based on the gene expression patterns. The goal of our phase II application is to take these diagnostic tests closer to the marketplace. We have the following four specific aims: I. We will expand our microarray analysis using a larger cohort of individuals with diabetes from different racial backgrounds (Caucasian, African-American, and Hispanic) and different geographical locations to validate our results and to further test the notion that two classes of type I diabetes exist in the human population. II. We propose to validate identity of clones that exhibit extremes in hybridization among the control and different disease groups and develop "mini-microarray" and quantitative PCR tests that distinguish among the different disease groups. III. We will test these platforms by analyzing blood samples from a large cohort of control and diabetic individuals. IV. We will validate the diagnostic test in a cohort of individuals with an initial diagnosis of hyperglycemia. 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. These include tests that classify diseases, predict severity, and predict optimal therapeutic options.

Thesaurus Terms:
diabetes mellitus, diagnostic test, gene expression, metabolism disorder diagnosis, microarray technology, technology /technique development diagnosis design /evaluation, geographic difference, human population genetics, hyperglycemia, racial /ethnic difference African American, Hispanic American, caucasian American, clinical research, human subject, questionnaire