title: Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cliniques Universitaires Saint-Luc and Université catholique de Louvain, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Gutierrez-Roelens
authors.forename: C
authors.initials: C
authors.lastname: Galant
authors.forename: I
authors.initials: I
authors.lastname: Theate
authors.forename: R J
authors.initials: RJ
authors.lastname: Lories
authors.forename: P
authors.initials: P
authors.lastname: Durez
authors.forename: A
authors.initials: A
authors.lastname: Nzeusseu-Toukap
authors.forename: B
authors.initials: B
authors.lastname: Van den Eynde
authors.forename: F A
authors.initials: FA
authors.lastname: Houssiau
authors.forename: B R
authors.initials: BR
authors.lastname: Lauwerys
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000069283:Rituximab; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab