TNF and rheumatoid arthritis: In addition, dissimilar gene clusters and distinct molecular signatures specifically expressed during early or long-standing RA suggest the involvement of different pathophysiological mechanisms in the disease course as a function of disease progression.38 In view of this, studies of early RA patient synovial tissue showed higher levels of TNFα-related gene expression, while long-standing RA patients had higher levels of IFN-response gene expression correlated with the downregulation of the metalloproteinase inhibitor gene and total protein biosynthesis.39