title: Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease-driven degradation as markers of gout and frequent gout attacks.
abstract: Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares.
  
  
  
  Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples from 447 men with gout collected at baseline from an ongoing clinical trial, were analysed by ELISA for neo-epitopes from MMP degradation of collagens type I (C1M) and type III (C3M). The log10 levels of both markers were compared between cases and controls and between gout patients with three or more gout attacks in the past year and those with two or less attacks.
  
  
  
  The circulating levels of C1M and C3M correlated with gout status in the case-control study. Levels of both markers were associated with frequent gout flares (⩾3 attacks in the past year) in both cohorts (odds ratio, OR = 3.1; 95% CI: 1.4, 6.8; P = 0.0056 for log10C1M, and OR = 6.7; 95% CI: 2.3, 19.3; P = 0.0005 for log10C3M). The area under the curve in a receiver operating characteristic analysis of frequent flares increased from 0.68 to 0.74 in one cohort and from 0.60 to 0.66 in the other when log10C1M and log10C3M were added to clinical variables of the model.
  
  
  
  C1M and C3M, reflective of interstitial matrix destruction, are associated with gout status and with frequent gout flares in men, suggesting that increased MMP activity may contribute to gout flares. Further research is needed to find out whether this is independent of dietary and lifestyle risk factors for acute gout.
authors.affiliation: Academic Rheumatology, Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham, UK Ana.Valdes@nottingham.ac.uk.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.affiliation: Rheumatology, Nordic Bioscience Biomarkers and Research, Herlev, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Manon-Jensen
authors.affiliation: Academic Rheumatology, Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Abhishek
authors.affiliation: Academic Rheumatology, Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Jenkins
authors.affiliation: Rheumatology, Nordic Bioscience Biomarkers and Research, Herlev, Denmark.
authors.forename: Anne Sofie
authors.initials: AS
authors.lastname: Siebuhr
authors.affiliation: Rheumatology, Nordic Bioscience Biomarkers and Research, Herlev, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.affiliation: Academic Rheumatology, Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Doherty
authors.affiliation: Academic Rheumatology, Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
authors.forename: Weiya
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Academic Rheumatology, Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Richardson
authors.affiliation: Academic Rheumatology, Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
authors.affiliation: Rheumatology, Nordic Bioscience Biomarkers and Research, Herlev, Denmark.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D000939:Epitopes; D006073:Gout / Q000201:enzymology*; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D024061:Collagen Type III; D000939:Epitopes; D020782:Matrix Metalloproteinases
keywords: biochemical markers; collagen neoepitopes; flares; gout; inflammation; interstitial matrix; matrix metalloprotease; tissue degradation