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Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment.
Arthritis Res Ther. 2010; 12(1):R11.AR

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.

Authors+Show Affiliations

Department of Pathology, VU University Medical Center, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands. e.g.vanbaarsen@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20096109

Citation

van Baarsen, Lisa Gm, et al. "Regulation of IFN Response Gene Activity During Infliximab Treatment in Rheumatoid Arthritis Is Associated With Clinical Response to Treatment." Arthritis Research & Therapy, vol. 12, no. 1, 2010, pp. R11.
van Baarsen LG, Wijbrandts CA, Rustenburg F, et al. Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment. Arthritis Res Ther. 2010;12(1):R11.
van Baarsen, L. G., Wijbrandts, C. A., Rustenburg, F., Cantaert, T., van der Pouw Kraan, T. C., Baeten, D. L., Dijkmans, B. A., Tak, P. P., & Verweij, C. L. (2010). Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment. Arthritis Research & Therapy, 12(1), R11. https://doi.org/10.1186/ar2912
van Baarsen LG, et al. Regulation of IFN Response Gene Activity During Infliximab Treatment in Rheumatoid Arthritis Is Associated With Clinical Response to Treatment. Arthritis Res Ther. 2010;12(1):R11. PubMed PMID: 20096109.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment. AU - van Baarsen,Lisa Gm, AU - Wijbrandts,Carla A, AU - Rustenburg,François, AU - Cantaert,Tineke, AU - van der Pouw Kraan,Tineke Ctm, AU - Baeten,Dominique L, AU - Dijkmans,Ben Ac, AU - Tak,Paul P, AU - Verweij,Cornelis L, Y1 - 2010/01/22/ PY - 2009/06/11/received PY - 2009/12/10/revised PY - 2010/01/22/accepted PY - 2010/1/26/entrez PY - 2010/1/26/pubmed PY - 2010/8/14/medline SP - R11 EP - R11 JF - Arthritis research & therapy JO - Arthritis Res Ther VL - 12 IS - 1 N2 - 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. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/20096109/Regulation_of_IFN_response_gene_activity_during_infliximab_treatment_in_rheumatoid_arthritis_is_associated_with_clinical_response_to_treatment_ L2 - https://arthritis-research.biomedcentral.com/articles/10.1186/ar2912 DB - PRIME DP - Unbound Medicine ER -