Regulation of interferon response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment

INTRODUCTION: Cross-regulation between tumor necrosis factor (TNF) and type I interferon (IFN) has been postulated to play an important role in autoimmune diseases. Therefore we determined the effect of TNF-blockade in rheumatoid arthritis (RA) on the type I IFN-response gene activity in relation to clinical response. METHODS: Peripheral blood from 33 RA patients was collected in PAXgene tubes before and after the start of infliximab treatment. In a first group of 15 patients the baseline expression of type I IFN-regulated genes was determined using cDNA-microarrays and compared to levels one month after treatment. The remaining 18 patients were studied as an independent group for validation using quantitative (q)PCR. RESULTS: Gene expression analysis revealed that anti-TNF antibody treatment induced a significant increase in type I IFN-response activity in a subset of RA patients, whereas expression levels remained similar or were slightly decreased in others. The findings appear clinically relevant since patients with an increased IFN-response gene activity after anti-TNF therapy had a poor clinical outcome. This association was confirmed and extended for an IFN-response gene set consisting of OAS1, LGALS3BP, Mx2, OAS2 and SERPING1 in five EULAR good and five EULAR poor responders, by qPCR. CONCLUSIONS: Regulation of IFN-response gene activity upon TNF-blockade in RA is not as consistent as previously described, but varies between patients. The differential changes in IFN-response gene activity appear relevant to the clinical outcome of TNF-blockade in RA