title: Effects of Rituximab and Infliximab Treatment on Carboxypeptidase B and Its Substrates in RA Synovium.
abstract: We evaluated the synovial effects of 2 potent biologic rheumatoid arthritis (RA) therapies, focusing on their effect on the expression level of carboxypeptidase B (CPB) and its substrates.
  
  
  
  Patients with RA receiving infliximab (IFX; n = 9) or rituximab (RTX; n = 5) had an arthroscopic synovial biopsy at baseline and 16 weeks posttherapy. Expression of CPB, C5a, osteopontin (OPN), CD3, CD20, CD55, and CD68 was assessed by immunohistochemistry and image analysis, and compared with OA synovium. RA disease activity score was assessed at multiple timepoints. Serial serum samples were analyzed for soluble CPB and C5a levels.
  
  
  
  The baseline clinical characteristics of patients receiving IFX and RTX were similar. At the time of the second biopsy, 50% of patients had achieved a European League Against Rheumatism good or moderate response. At baseline, expression of CPB, C5a, and OPN was markedly higher in RA compared with OA synovium and correlated with mononuclear cell infiltration. There was an overall reduction in synovial expression of CPB, C5a, and OPN paralleling a reduction in mononuclear cell infiltration, but these changes were not associated with clinical response. After an early reduction in serum C5a levels, these returned to baseline levels at later timepoints.
  
  
  
  In response to IFX and RTX treatment, RA synovial expression of CPB, C5a, and OPN decrease independently of the clinical response, reflecting the complex proinflammatory and antiinflammatory effects of this pathway.
authors.affiliation: From the Department of Internal Medicine and Department of Surgery, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.S. Edginton, BSc, Department of Internal Medicine, University of Manitoba; C.A. Hitchon, MD, FRCPC, Department of Internal Medicine, University of Manitoba; W. Froese*, MD, FRCSC, Department of Surgery, University of Manitoba; H. El-Gabalawy, MD, FRCPC, Department of Internal Medicine, University of Manitoba. stefanedginton@gmail.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Edginton
authors.affiliation: From the Department of Internal Medicine and Department of Surgery, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.S. Edginton, BSc, Department of Internal Medicine, University of Manitoba; C.A. Hitchon, MD, FRCPC, Department of Internal Medicine, University of Manitoba; W. Froese*, MD, FRCSC, Department of Surgery, University of Manitoba; H. El-Gabalawy, MD, FRCPC, Department of Internal Medicine, University of Manitoba.
authors.forename: Carol
authors.initials: C
authors.lastname: Hitchon
authors.affiliation: From the Department of Internal Medicine and Department of Surgery, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.S. Edginton, BSc, Department of Internal Medicine, University of Manitoba; C.A. Hitchon, MD, FRCPC, Department of Internal Medicine, University of Manitoba; W. Froese*, MD, FRCSC, Department of Surgery, University of Manitoba; H. El-Gabalawy, MD, FRCPC, Department of Internal Medicine, University of Manitoba.
authors.forename: Warren
authors.initials: W
authors.lastname: Froese
authors.affiliation: From the Department of Internal Medicine and Department of Surgery, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.S. Edginton, BSc, Department of Internal Medicine, University of Manitoba; C.A. Hitchon, MD, FRCPC, Department of Internal Medicine, University of Manitoba; W. Froese*, MD, FRCSC, Department of Surgery, University of Manitoba; H. El-Gabalawy, MD, FRCPC, Department of Internal Medicine, University of Manitoba.
authors.forename: Hani
authors.initials: H
authors.lastname: El-Gabalawy
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D043424:Carboxypeptidase B / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000494:pharmacology* / Q000627:therapeutic use; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D000069283:Rituximab; D000069285:Infliximab; D043424:Carboxypeptidase B
keywords: BIOLOGIC THERAPIES; CARBOXYPEPTIDASE B; RHEUMATOID ARTHRITIS; SYNOVIUM