Tomas Weitoft1, Anders Larsson2, Vivek A Manivel3, Jörgen Lysholm4, Ann Knight5, Johan Rönnelid3. 1. Section of Rheumatology, Center of Research and Development, Uppsala University/County Council of Gävleborg, tomas.weitoft@lg.se. 2. Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala. 3. Department of Immunology, Genetics and Pathology, Uppsala University. 4. Clinic of Rheumatology, Falun Hospital, Falun and. 5. Section of Rheumatology, Department of Medical Sciences, Uppsala University Hospital, Sweden.
Abstract
OBJECTIVES: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF. METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3. RESULTS: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients. CONCLUSION: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.
OBJECTIVES:Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RApatients with and without ACPA and RF. METHODS: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3. RESULTS:SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients. CONCLUSION: The differences in cathepsin S and cathepsin L between RApatients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.
Authors: Patrick Hargreaves; Douglas Daoudlarian; Michel Theron; Fabrice A Kolb; Marianne Manchester Young; Bernhard Reis; Andre Tiaden; Bettina Bannert; Diego Kyburz; Tobias Manigold Journal: Arthritis Res Ther Date: 2019-07-18 Impact factor: 5.156
Authors: Tomas Weitoft; Johan Rönnelid; Azita Sohrabian; Linda Mathsson-Alm; Monika Hansson; Ann Knight; Jörgen Lysholm; Martin Cornillet; Karl Skriner; Guy Serre; Anders Larsson Journal: Ann Rheum Dis Date: 2018-06-12 Impact factor: 19.103
Authors: Dan Zhao; Laela M Hajiaghamohseni; Xiang Liu; Zdzislaw M Szulc; Aiping Bai; Alicja Bielawska; James S Norris; Sakamuri V Reddy; Yusuf A Hannun; Azizul Haque Journal: Cytokine Date: 2020-07-29 Impact factor: 3.861