Whether TNF inhibition has divergent effects on key gene networks in these three diseases. Over the past decade, investigators have turned to microarray analytic techniques of peripheral blood cells and target tissues to examine cross-sectional and longitudinal gene expression. From these studies, several fundamental insights emerged. First, the molecular network in the immune mediated inflammatory disorders is far more complex than expected. Second, cross-sectional differential gene expression is much lower in blood cells and in specific cell lineages compared to whole tissues. Third, gene expression signatures in blood cells and synovial biopsies are heterogeneous and very patient-specific. Fourth, to date, no pre-GS-5734 AbMole treatment gene expression profile in blood or tissue can accurately and reliably predict response to anti-TNF therapy in any of these three diseases. Despite these caveats, microarray studies in autoimmune disorders reveal shared perturbations of common cellular processes, particularly apoptosis, regulation of cytokines and T cell activation. Taken together, microarray studies reveal a complex, heterogeneous immune inflammatory response in the immune mediated inflammatory diseases yet common signatures, as outlined above, are characteristic of specific autoimmune diseases. Given the marked effects of TNF inhibition on patient reported outcomes, systemic inflammation and tissue remodeling in RA, PsA and Ps, genomic analysis of cells and tissues before and after treatment has the potential to unveil pivotal overlapping and disease-specific transcriptional events in disease pathogenesis. The immune mediated inflammatory diseases RA, PsA and Ps have divergent phenotypes but share several pathologic features that include overproduction of TNF and other cytokines, along with cellular proliferation and tissue remodeling. They also have overlapping metabolic and cardiovascular comorbidities and demonstrate, on average, good to excellent responses to antiTNF agents. We hypothesized that the genomic response to antiTNF agents in these three diseases would be distinct and would vary in the different cell types and target tissues. To our knowledge, this is the first study of differential gene expression in discrete populations of monocytes and immune cells that also examined expression in target tissues following treatment with IFX. Moreover, the response in RA was clustered around the 2 week time point whereas the most notable effect on gene expression in PsA and Ps was at 10 weeks. In Ps biopsies, a large number of genes were dramatically down-regulated by IFX at 2 weeks but the gene expression profile in skin from patients with excellent clinical responses was still significantly different from uninvolved skin.