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Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.

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Gutierrez-Roelens, Ilse [UCL] Galant, Christine [UCL] Théate, Ivan [UCL] Lories, Rik J. [UCL] Durez, Patrick [UCL] Nzeusseu Toukap, Adrien [UCL] Van den Eynde, Benoît [UCL] Houssiau, Frédéric [UCL] Lauwerys, Bernard [UCL]

(eng) OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Access type Accès restreint
Publication date 2011
Language Anglais
Journal information "Arthritis & Rheumatism" - Vol. 63, no. 5, p. 1246-1254 (2011)
Peer reviewed yes
Publisher JohnWiley & Sons, Inc. ((United States) Hoboken)
issn 0004-3591
e-issn 1529-0131
Publication status Publié
Affiliations UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales
UCL - (SLuc) Service de rhumatologie
UCL - (SLuc) Service d'anatomie pathologique
UCL - SSS/IREC/MORF - Pôle de Morphologie
MESH Subject Antibodies, Monoclonal, Murine-Derived - pharmacology, therapeutic use ; Antirheumatic Agents - pharmacology, therapeutic use ; Synovial Membrane - drug effects, immunology ; Arthritis, Rheumatoid - drug therapy, genetics, immunology ; Female ; Gene Expression - drug effects, immunology ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction
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Bibliographic reference Gutierrez-Roelens, Ilse ; Galant, Christine ; Théate, Ivan ; Lories, Rik J. ; Durez, Patrick ; et. al. Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.. In: Arthritis & Rheumatism, Vol. 63, no. 5, p. 1246-1254 (2011)
Permanent URL http://hdl.handle.net/2078.1/105278