Figure 2

Pre-treatment expression of TLR, RIG-I and IFN-beta pathway genes compared between the two patient groups. The pathways that induce type I IFN expression via TRAF3 and MyD88 are shown on the left and the pathway that is triggered by IFN-beta (JAK/STAT pathway) is shown on the right. Each gene is colored by the magnitude of mean expression difference between the MX1_high group (n = 7) and the MX1_low group (n = 30). Black node labels indicate significant differences (P-value < 0.01). Aside from MX1 as an established biomarker of IFN activity, other ISGs also showed higher levels of expression in the MX1_high patient cohort before initiation of subcutaneous IFN-beta therapy. The elevated endogenous IFN-like activity of these patients is likely the result of elevated amounts of the transcription factors STAT1, STAT2 and IRF9, which form the ISGF3 complex. DNA-binding sites for this complex can be found in the promoters of RIG-I-like helicases (IFIH1, DDX58), suppressor of cytokine signaling (SOCS) genes and the transcription factor IRF7, which were also expressed at higher levels in MX1_high patients (see Additional file 3). Other genes such as IRF3, the NFkappaB members, IFNB1 and the IFN-alpha/beta receptors were not differentially expressed.