Analysis of human immune mediated diseases and their murine models by gene expression profiling
Autoimmune and atopic diseases are immune-mediated multigenic diseases. The work of this thesis tests the hypothesis of performing gene expression profiling using peripheral blood mononuclear cells as a common source to characterize distinct human diseases. Our studies demonstrate that distinct gene expression profiles exist in both human autoimmune and atopic diseases. The unique gene expression profile in autoimmune disease is composed of two parts; one is genetic, second results from disease onset. A unique gene expression profile is also present in atopic disease and a portion of this profile may be used to monitor responses to therapy. In addition, we demonstrate it is possible to use gene expression profiling as a prognostic factor. In parallel, a specific gene expression profile exists in T cells in a human type I diabetes murine model-NOD. However, the NOD profile is not shared with the common autoimmune disease profile, but predicts a common liability, lymphopenia, which may stimulate autoimmunity. In summary, the studies of this thesis demonstrate that the gene expression profiling method is a powerful tool to depict the molecular portraits of immune-mediated diseases.