[en] Abstract Objective. Plasma and synovial myeloperoxidase (MPO) and its products were strongly associated with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, it is well known that there is a link between oxidative stress and cytokines. The present study aims at investigating the link between synovial MPO (and its products), interleukin (IL)-18, which is involved in the degradation of articular cartilage in RA, and IL-8, which is involved in recruitment and activation of neutrophils during inflammation. Effects of the treatment of RA on the biological parameters were also investigated. Methods. Patients (n = 105) were studied including 39 patients with OA, 33 with RA and 33 with RA receiving a specific treatment. Disease activity score (DAS-28) was calculated whereas MPO antigen/activity, neutrophils, chloro-tyrosine (Cl-Tyr), homocitrulline (Hcit), IL-8, and IL-18 were measured in synovial fluid (SF) and CRP was measured in serum. Results. DAS-28 and CRP levels were not significantly different between groups. MPO activity, and MPO, Cl-Tyr, and Hcit levels were significantly higher in SF of RA patients than OA patients. MPO specific activity (MPO activity/antigen ratio) was significantly lower in treated than in untreated RA patients as was IL-8. MPO activity and concentration were correlated with IL-8 and IL-18 in untreated but not in treated RA patients. Conclusions. MPO level is related to IL-8 and IL-18 levels in untreated RA patients. A link has been shown between treatment and decrease of IL-8, MPO specific activity and Hcit in SF. The causal role of MPO in SF inflammation and how treatment can affect MPO specific activity need further investigations.
Research center :
CORD - Centre de l'Oxygène, Recherche et Développement - ULiège
Disciplines :
Immunology & infectious disease
Author, co-author :
Nzeusseu Toukap, A.; Université Catholique de Louvain - UCL
Delporte, C.; Université Libre de Bruxelles - ULB
Noyon, C.; Université Libre de Bruxelles - ULB
Franck, Thierry ; Université de Liège - ULiège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Anesthésiologie gén. et pathologie chirurg. des grds animaux
Rousseau, A.; Université Libre de Bruxelles - ULB
Serteyn, Didier ; Université de Liège - ULiège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Anesthésiologie gén. et pathologie chirurg. des grds animaux
Raes, M.; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
Vanhaeverbeek, M.; Université Libre de Bruxelles - ULB
Moguilevsky, N.; Facultés Universitaires Notre-Dame de la Paix - Namur - FUNDP
Neve, J.; Université Libre de Bruxelles - ULB
Vanhamme, L.; Université Libre de Bruxelles - ULB
Durez, P.; Université Catholique de Louvain - UCL
Van Antwerpen; Université Libre de Bruxelles - ULB
Zouaoui Boudjeltia, K.; Université Libre de Bruxelles - ULB
Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum 2008; 58: 15-25.
Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum 2008; 58: 26-35.
Wruck CJ, Fragoulis A, Gurzynski A, Brandenburg LO, Kan YW, Chan K, et al. Role of oxidative stress in rheumatoid arthritis: Insights from the Nrf2-knockout mice. Ann Rheum Dis 2011; 70: 844-850.
Steinbeck MJ, Nesti LJ, Sharkey PF, Parvizi J. Myeloperoxidase and chlorinated peptides in osteoarthritis: Potential biomarkers of the disease. J Orthop Res 2007; 25: 1128-1135.
Mydel P, Wang Z, Brisslert M, Hellvard A, Dahlberg LE, Hazen SL, Bokarewa M. Carbamylation-dependent activation of T cells: A novel mechanism in the pathogenesis of autoimmune arthritis. J Immunol 2010; 184: 6882-6890.
Fernandes RM, da Silva NP, Sato EI. Increased myeloperoxidase plasma levels in rheumatoid arthritis. Rheumatol Int 2012; 32: 1605-1609.
Stamp LK, Khalilova I, Tarr JM, Senthilmohan R, Turner R, Haigh RC, et al. Myeloperoxidase and oxidative stress in rheumatoid arthritis. Rheumatology 2012; 51: 1796-1803.
Dai SM, Shan ZZ, Xu H, Nishioka K. Cellular targets of interleukin-18 in rheumatoid arthritis. Ann Rheum Dis 2007; 66: 1411-1418.
Hammond ME, Lapointe GR, Feucht PH, Hilt S, Gallegos CA, Gordon CA, et al. IL-8 induces neutrophil chemotaxis predominantly via type I IL-8 receptors. J Immunol 1995; 155: 1428-1433.
Park HJ, Kim SS, Lee SY, Park NH, Park JY, Choi YJ, Jeon HJ. A practical MRI grading system for osteoarthritis of the knee: Association with Kellgren-Lawrence radiographic scores. Eur J Radiol 2013; 82: 112-117.
Wells G, Becker JC, Teng J, Dougados M, SchiffM, Smolen J, et al. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann Rheum Dis 2009; 68: 954-960.
Franck T, Kohnen S, Boudjeltia KZ, Van Antwerpen P, Bosseloir A, Niesten A, et al. A new easy method for specific measurement of active myeloperoxidase in human biological fl uids and tissue extracts. Talanta 2009; 80: 723-729.
Delporte C, Franck T, Noyon C, Dufour D, Rousseau A, Madhoun P, et al. Simultaneous measurement of proteinbound 3-chlorotyrosine and homocitrulline by LC-MS/MS after hydrolysis assisted by microwave: Application to the study of myeloperoxidase activity during hemodialysis. Talanta 2012; 99: 603-609.
Attur MG, Dave M, Akamatsu M, Katoh M, Amin AR. Osteoarthritis or osteoarthrosis: The definition of infl ammation becomes a semantic issue in the genomic era of molecular medicine. Osteoarthritis Cartilage 2002; 10: 1-4.
Sokolov AV, Ageeva KV, Pulina MO, Cherkalina OS, Samygina VR, Vlasova II, et al. Ceruloplasmin and myeloperoxidase in complex affect the enzymatic properties of each other. Free Radic Res 2008; 42: 989-998.
Van Antwerpen P, Slomianny MC, Boudjeltia KZ, Delporte C, Faid V, Calay D, et al. Glycosylation pattern of mature dimeric leukocyte and recombinant monomeric myeloperoxidase: Glycosylation is required for optimal enzymatic activity. J Biol Chem 2010; 285: 16351-16359.
Cross AS, Wright DG. Mobilization of sialidase from intracellular stores to the surface of human neutrophils and its role in stimulated adhesion responses of these cells. J Clin Invest 1991; 88: 2067-2076.
Wang Z, Nicholls SJ, Rodriguez ER, Kummu O, Horkko S, Barnard J, et al. Protein carbamylation links infl ammation, smoking, uremia and atherogenesis. Nat Med 2007; 13: 1176-1184.