Eloisa Romano1, Riccardo Terenzi2, Mirko Manetti2, Francesca Peruzzi2, Ginevra Fiori2, Francesca Nacci2, Silvia Bellando-Randone2, Marco Matucci-Cerinic2, Serena Guiducci2. 1. 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. 2. 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.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Nadia M T Roodenrijs; Paco M J Welsing; Joël van Roon; Jan L M Schoneveld; Marlies C van der Goes; György Nagy; Michael J Townsend; Jacob M van Laar Journal: Rheumatology (Oxford) Date: 2022-08-30 Impact factor: 7.046