At the same time, patients with a “low” baseline IFN signature who did not respond to anti-TNF blockade, showed an increase in type I IFN response gene expression by the end of treatment,28 indicating that neutralization of TNFα in these patients favours the upregulation of genes that were previously silenced by TNFα.29 Alternatively, the upregulation in IFN bioactivity has also been suggested to be deleterious in RA or to represent a failed attempt to counter-regulate inflammation.25 The gene discussed is TNF; the disease is rheumatoid arthritis.