An increased expression and activation of IFN-inducible genes, known as interferon signature, has been reported in SSc44 and several interferon regulatory factors (IRFs), including IRF5, IRF4, and IRF8, have been involved in its susceptibility14,45, thus supporting the role of IRF1, previously associated with CD but not with SSc, as a new susceptibility gene for this last condition. Here, IRF4 is linked to systemic sclerosis.