Myeloperoxidase and its products in synovial fluid of patients with treated or untreated rheumatoid arthritis

Toukap, A. Nzeusseu; Delporte, Cédric; Noyon, Caroline; Franck, Thierry; Rousseau, Alexandre Fontaine; Serteyn, Didier; Raes, Martine; Vanhaeverbeek, Michel; Moguilevsky, Nicole; Nève, Jean; Vanhamme, Luc; Durez, Patrick; Antwerpen, Pierre Van; Boudjeltia, Karim Zouaoui

doi:10.3109/10715762.2014.886327

Cited by 37 publications

(24 citation statements)

References 18 publications

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“…Carbamylation is a chemical reaction mediated by cyanate that modifies lysine residues [5]. Normally the level of cyanate is in equilibrium with urea but specific conditions like inflammation can warp this equilibrium through a myeloperoxidase-dependent mechanism [8, 9]. This leads to the local increase of cyanate levels, thus empowering the degree of carbamylation [10].…”

Section: Introductionmentioning

confidence: 99%

Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases

et al. 2016

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BackgroundAntibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs).MethodsSerum samples (n = 607) from 309 patients with RA, 200 disease controls and 98 normal healthy subjects (NHS) were evaluated. Anti-CarP were detected using carbamylated fetal calf serum as the antigen. ACPAs were detected using second-generation ELISA and IgM RF was assessed as part of routine analysis.ResultsAnti-CarP antibodies were detected in 117 patients with RA (34.4%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were detected in 33 patients (16.5%), ACPA in 29 patients (14.5%) and RF in 64 patients (32%). In particular, 16.8% of patients with systemic lupus erythematosus and 31.1% of patients with Sjögren syndrome were positive for anti-CarP. The sensitivity of anti-CarP, ACPA and RF was 46.8%, 61.8% and 64.4%, respectively and specificity was 91.95%, 89.93% and 76.51%, respectively.ConclusionsThe present study extends the knowledge of anti-CarP antibodies, confirming previous data on the diagnostic accuracy of anti-CarP in RA in a large cohort of Italian patients. Anti-CarP antibodies demonstrated relatively low sensitivity and slightly higher specificity compared to ACPA and RF. Even if predominantly present in RA, anti-CarP was detected in a variable percentage of patients with other autoimmune rheumatic diseases and their generation could be attributed to the inflammatory status; the clinical relevance of anti-CarP antibodies in these latter patients should be further determined.

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Section: Introductionmentioning

confidence: 99%

Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases

et al. 2016

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“…When the rate of oxidants production surpasses the capability of antioxidant systems to eliminate these oxidants products, oxidative stress ensues, which leads to subsequent injury to cells and tissues . Previous clinical studies have shown increased prooxidant and oxidative activities, along with decreased antioxidant defence activities in patients with RA …”

Section: Introductionmentioning

confidence: 95%

Association of oxidative stress with clinical characteristics in patients with rheumatoid arthritis

Kardeş

Karagülle

Durak

et al. 2017

Eur J Clin Investigation

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Background: Few studies examining the association between oxidative stress and clinical parameters or disease activity in patients with rheumatoid arthritis (RA) are available. Therefore, the objective of this study was to test whether oxidative stress has any association with clinical parameters and disease activity in patients with RA. Materials and methods: In this post hoc cross-sectional study, 45 patients with RA treated with traditional disease-modifying antirheumatic drugs (DMARDs) AE low-dose glucocorticoids AE nonsteroidal analgesics for at least 3 months were analysed. Oxidative stress parameters were malondialdehyde (MDA), superoxide dismutase (SOD), antioxidant potential (AOP) and nonenzymatic superoxide radical scavenger activity (NSSA). Clinical parameters were pain, patient global assessment, physician global assessment, Health Assessment Questionnaire (HAQ), and disease activity score (DAS28). Results: Plasma NSSA levels were significantly inversely correlated with tender joints count (r = À.304; P = .042), swollen joints count (r = À.342; P = .021) and DAS28 (r = À.396; P = .009). There were no significant correlations between MDA/SOD/AOP and any of clinical parameters or DAS28 (P > .05 for all). Multiple regression analysis revealed that NSSA was an independent variable of DAS28 (b=À.243, P = .016). Conclusion:The preliminary results demonstrate that plasma NSSA levels were inversely correlated with tender and swollen joints count and DAS28 and that NSSA was independently associated with DAS28, in patients with RA treated with traditional DMARDs; and provide initial support that NSSA may be used as a biomarker of disease activity in patients with RA.

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“…However, there was inconsistency as to the correlation between MPO levels in the plasma and disease activity score, as one study showed correlation, while another did not [83,84]. Additionally, RA patients exhibited higher levels of MPO and its product Cl-Tyr in synovial fluids compared to osteoarthritis (OA) patients [85]. RA patients treated with disease-modifying antirheumatic drugs and/or biological agents exhibited decreased MPO-specific activity in the joints [85].…”

Section: Mpo and Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

“…Additionally, RA patients exhibited higher levels of MPO and its product Cl-Tyr in synovial fluids compared to osteoarthritis (OA) patients [85]. RA patients treated with disease-modifying antirheumatic drugs and/or biological agents exhibited decreased MPO-specific activity in the joints [85]. These data correlate well with murine studies, where injection of active or inactive MPO into the joints exacerbated disease, while decreased MPO levels in affected joints, observed after treatment with atrovastatin or blockade of CXCR1/CXCR2 receptors, correlated with decreased severity disease [86–88].…”

Section: Mpo and Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

Myeloperoxidase: A new player in autoimmunity

Strzępa

Pritchard

Dittel

2017

Cellular Immunology

175

103

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Myeloperoxidase (MPO) is the most toxic enzyme found in the azurophilic granules of neutrophils. MPO utilizes H2O2 to generate hypochlorous acid (HClO) and other reactive moieties, which kill pathogens during infections. In contrast, in the setting of sterile inflammation, MPO and MPO-derived oxidants are thought to be pathogenic, promoting inflammation and causing tissue damage. In contrast, evidence also exists that MPO can limit the extent of immune responses. Elevated MPO levels and activity are observed in a number of autoimmune diseases including in the central nervous system (CNS) of multiple sclerosis (MS) and the joints of rheumatoid arthritis (RA) patients. A pathogenic role for MPO in driving autoimmune inflammation was demonstrated using mouse models. Mechanisms whereby MPO is thought to contribute to disease pathogenesis include tuning of adaptive immune responses and/or the induction of vascular permeability.

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Myeloperoxidase and its products in synovial fluid of patients with treated or untreated rheumatoid arthritis

Cited by 37 publications

References 18 publications

Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases

Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases

Association of oxidative stress with clinical characteristics in patients with rheumatoid arthritis

Myeloperoxidase: A new player in autoimmunity

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