These data suggest that although TNF is of central importance in all three diseases based on the excellent clinical responses, the pathways modulated by TNF differ suggesting distinct disease mechanisms. Finally, a number of key transcriptional regulators were either activated or suppressed after treatment but little overlap was observed between the disorders in terms of specific regulators involved. Overall, analysis of peripheral blood resulted in significant gene lists that were not maintained following corrections for multiple comparisons. As a result, determination of specific transcription factor involvement in blood was also limited. The gene signature for PsA was different than RA. In another study, Stoeckman et al. found 310 differentially expressed genes in 16 PsA patients compared to controls, most of which were upregulated. The signature differed from those found in RA and SLE but interestingly showed little overlap with Batliwalla et al.. We cannot directly compare our findings with these 2 studies, since we examined the change in gene expression after IFX, but we did not see overlap with our gene lists and these two data sets. The reason for the higher number of differential gene expression in PsA compared to RA and Ps after IFX may relate to the fact that inflammatory cells that transit to both the skin and joint may be triggered by an array of signals that activate numerous gene networks. Further study is required to address this finding, however. It is important to note that the numbers of differentially expressed genes do not always correspond to enriched pathways derived from gene lists which are dependent on specific genes that comprise the pathway. The results from the pathway analysis support a disease paradigm put forth by McGonagle et al. in which RA pathogenesis is Remdesivir GS-5734 mediated largely by acquired immune mechanisms, PsA primarily by the innate immune response, and Ps by a combination of acquired and innate pathways, but further studies with larger sample sizes are required to confirm this model. Our study is the first examination of differential gene expression in cell populations and target tissues from different immune mediated inflammatory disorders but several limitations must be considered. First, the low number of synovial samples in diseases with heterogeneous tissue responses does not provide a comprehensive assessment of the joint response although the relationship between differential gene regulation in the joint and skin of an individual patient is informative. Second, we do not have confirmatory immunohistochemistry data on tissue expression of differentially expressed genes determined by microarray. Third that may be responsible for persistent inflammation following treatment.