title: Disease activity improvement in rheumatoid arthritis treated with tumor necrosis factor-α inhibitors correlates with increased soluble Fas levels.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia. Tumor necrosis factor-α (TNF-α) plays a pivotal role in RA by interfering with the Fas-Fas ligand (FasL) proapoptotic pathway. We investigated the circulating levels of soluble Fas (sFas) and soluble FasL (sFasL), and their possible correlation with disease activity and improvement after anti-TNF-α treatment in RA.
  
  
  METHODS
  Serum levels of sFas and sFasL were measured by quantitative ELISA in 52 patients with RA before and after 3 months of anti-TNF-α treatment (adalimumab, n = 32; infliximab, n = 20). Disease activity measures [Disease Activity Score at 28 joints-erythrocyte sedimentation rate (DAS28-ESR), C-reactive protein (CRP)] were recorded before and after treatment. Forty age-matched and sex-matched healthy subjects served as controls.
  
  
  RESULTS
  No significant differences in serum sFas levels were detected between anti-TNF-α-naive patients with RA and controls. After anti-TNF-α treatment, serum sFas levels significantly increased in patients with RA compared to both anti-TNF-α-naive patients and controls. Increased sFas levels inversely correlated with disease activity variables (DAS28-ESR: r = -0.739, CRP: r = -0.636, both p < 0.001). No significant differences in sFasL levels were detected in patients with RA before and after anti-TNF-α treatment.
  
  
  CONCLUSIONS
  In RA, an increase in sFas levels closely correlates with improvement in disease activity induced by TNF-α inhibitors, suggesting their ability to modulate Fas-mediated synoviocyte apoptosis.
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence. eloisaromano@libero.it.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Romano
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Terenzi
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence.
authors.forename: Mirko
authors.initials: M
authors.lastname: Manetti
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence.
authors.forename: Francesca
authors.initials: F
authors.lastname: Peruzzi
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence.
authors.forename: Ginevra
authors.initials: G
authors.lastname: Fiori
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nacci
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bellando-Randone
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence.
authors.forename: Marco
authors.initials: M
authors.lastname: Matucci-Cerinic
authors.affiliation: From the Department of Experimental and Clinical Medicine, Section of Internal Medicine; Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.E. Romano, PhD; R. Terenzi, MD; F. Peruzzi, MD; G. Fiori, MD; F. Nacci, MD; S. Bellando-Randone, MD, PhD; M. Matucci-Cerinic, MD, PhD; S. Guiducci, MD, PhD, Department of Experimental and Clinical Medicine, Section of Internal Medicine, Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi; DENOthe Centre; M. Manetti, PhD; Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence.
authors.forename: Serena
authors.initials: S
authors.lastname: Guiducci
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D019014:fas Receptor / Q000097:blood*
chemical_list: D018501:Antirheumatic Agents; C491901:FAS protein, human; D053222:Fas Ligand Protein; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000069285:Infliximab; D000068879:Adalimumab
keywords: APOPTOSIS; DISEASE ACTIVITY; RHEUMATOID ARTHRITIS; SOLUBLE FAS; TNF-α INHIBITORS