Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Regulation of IFN Response Gene Activity During Infliximab Treatment in Rheumatoid Arthritis Is Associated with Clinical Response to Treatment
Van Baarsen1, Lisa G.M., Wijbrandts2, Carla A., Rustenburg1, Francois, Cantaert2, Tineke, van der Pouw Kraan1, Tineke C.T.M., Baeten2, Dominique L., Dijkmans1, Ben A.C.
Cross-regulation between TNF and type I 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.
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 used as an independent group for validation using quantitative (q)PCR.
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 anti-TNF induced increased IFN-response gene activity 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.
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.
This study was supported by grants from The Netherlands Organization for Health Research and Development (ZonMw) in assignment of The Netherlands Organization for Scientific Research (NWO: grant number 945-02-029), the European Community's FP6 funding (Autocure), the Innovation Oriented research Program (IOP) on Genomics and the Centre for Medical Systems Biology (Netherlands Genomics Initiative). This publication reflects only the authors' views. The European Community is not liable for any use that may be made of the information herein.
To cite this abstract, please use the following information:
Van Baarsen, Lisa G.M., Wijbrandts, Carla A., Rustenburg, Francois, Cantaert, Tineke, van der Pouw Kraan, Tineke C.T.M., Baeten, Dominique L., et al; Regulation of IFN Response Gene Activity During Infliximab Treatment in Rheumatoid Arthritis Is Associated with Clinical Response to Treatment [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1341