Research article

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

Lisa GM van Baarsen^1,2, Carla A Wijbrandts³, François Rustenburg¹, Tineke Cantaert³, Tineke CTM van der Pouw Kraan⁴, Dominique L Baeten³, Ben AC Dijkmans⁵, Paul P Tak³ and Cornelis L Verweij^1,5*

• * Corresponding author: Cornelis L Verweij c.verweij@vumc.nl

Author Affiliations

¹ Department of Pathology, VU University Medical Center, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands

² Current address: Department of Clinical Immunology & Rheumatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

³ Department of Clinical Immunology & Rheumatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

⁴ Department of Molecular Cell Biology & Immunology, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

⁵ Department of Rheumatology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

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Arthritis Research & Therapy 2010, 12:R11 doi:10.1186/ar2912

Published: 22 January 2010

Abstract

Introduction

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.

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 polymerase chain reaction (qPCR).

Results

Gene expression analysis revealed that anti-TNF antibody treatment induced a significant increase in type I IFN response gene 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.