Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium
Article first published online: 27 APR 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 5, pages 1246–1254, May 2011
How to Cite
Gutierrez-Roelens, I., Galant, C., Theate, I., Lories, R. J., Durez, P., Nzeusseu-Toukap, A., Van den Eynde, B., Houssiau, F. A. and Lauwerys, B. R. (2011), Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium. Arthritis & Rheumatism, 63: 1246–1254. doi: 10.1002/art.30292
- Issue published online: 27 APR 2011
- Article first published online: 27 APR 2011
- Accepted manuscript online: 17 FEB 2011 12:08PM EST
- Manuscript Accepted: 3 FEB 2011
- Manuscript Received: 30 MAY 2010
- Roche Belgium and by grants from the Fondation Saint-Luc (Cliniques Universitaires Saint-Luc)
- Fonds de la Recherche Scientifique et Médicale (Belgium)
- Fonds Spécial de Recherche (Communauté française de Belgique)
- Région Wallone (BioWin, Health Cluster of Wallonia)
- Flanders Research Foundation (FWO-Vlaanderen)
Rituximab displays therapeutic benefits in the treatment of patients with rheumatoid arthritis (RA) resistant to tumor necrosis factor (TNF) blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. We undertook this study to investigate the global molecular effects of rituximab in synovial biopsy samples obtained from anti-TNF–resistant RA patients before and after administration of the drug.
Paired synovial biopsy samples were obtained from the affected knee of anti-TNF–resistant RA patients before (time 0) and 12 weeks after (time 12) initiation of rituximab therapy. Total RNA was extracted, labeled according to standard Affymetrix procedures, and hybridized on GeneChip HGU133 Plus 2.0 slides. Immunohistochemistry and quantitative real-time reverse transcriptase–polymerase chain reaction experiments were performed to confirm the differential expression of selected transcripts.
According to Student's paired t-tests, 549 of 54,675 investigated probe sets were differentially expressed between time 0 and time 12. Pathway analysis revealed that genes down-regulated between time 0 and time 12 were significantly enriched in immunoglobulin genes and genes involved in chemotaxis, leukocyte activation, and immune responses (Gene Ontology annotations). In contrast, genes up-regulated between time 0 and time 12 were significantly enriched in transcripts involved in cell development (Gene Ontology annotation) and wound healing (Gene Set Enrichment Analysis). At baseline, higher synovial expression of immunoglobulin genes was associated with response to therapy.
Rituximab displays unique effects on global gene expression profiles in the synovial tissue of RA patients. These observations open new perspectives in the understanding of the biologic effects of the drug and in the selection of patients likely to benefit from this therapy.