title: Circulating citrullinated vimentin fragments reflect disease burden in ankylosing spondylitis and have prognostic capacity for radiographic progression.
abstract: OBJECTIVE
  Ankylosing spondylitis (AS) has been considered a seronegative rheumatic disease based on absent or low levels of antibodies against citrullinated proteins. The present study was undertaken to evaluate whether a citrullinated and matrix metalloproteinase-degraded fragment of vimentin (VICM) could be a prognostic biomarker in AS.
  
  
  METHODS
  VICM was measured in serum samples from healthy controls (n=35), control patients with rheumatoid arthritis (RA) (n=47), and patients with AS (n=201). The optimal cutoff for diagnostic sensitivity and specificity was determined by receiver operating characteristic curve analysis. Baseline and 2-year spine radiographs were available from 118 AS patients, and were scored using the modified Stoke AS Spine Score (mSASSS). We assessed correlations with patient demographic characteristics (age, disease duration), disease activity (Bath AS Disease Activity Index [BASDAI], C-reactive protein level), and disease severity (mSASSS) using Spearman's rho. The independent association of VICM with 2-year radiographic progression, defined as a change of >0 in the mSASSS or the development of a new syndesmophyte, was analyzed by multivariate regression.
  
  
  RESULTS
  Levels of degraded VICM were significantly higher in both RA patients and AS patients than in healthy controls (both P<0.001). AS patients with the highest levels of VICM had the largest burden of disease (P<0.01), i.e., highest mSASSS score and BASDAI. VICM levels were significantly and independently associated with radiographic progression after 2 years (β=0.69, P=0.0005). Patients with both a high VICM level and a high baseline mSASSS had the highest risk of radiographic progression (odds ratio 13 for mSASSS change, 32 for new syndesmophytes), with progression occurring in 67% of these patients.
  
  
  CONCLUSIONS
  The present findings show that serum VICM may be of prognostic value in AS. The data also suggest that citrullination may be relevant in AS pathogenesis.
authors.affiliation: Department of Rheumatology, Nordic Bioscience, Herlev, Denmark. acbj@nordicbioscience.com
authors.forename: Anne C
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: Efstathios
authors.initials: E
authors.lastname: Vassiliadis
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wichuk
authors.forename: Kathrine
authors.initials: K
authors.lastname: Marcher-Mikkelsen
authors.forename: Rik
authors.initials: R
authors.lastname: Lories
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Walter P
authors.initials: WP
authors.lastname: Maksymowych
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002956:Citrulline; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006867:Hydrolases; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D000076342:Protein-Arginine Deiminases; D012372:ROC Curve; D011859:Radiography; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D014746:Vimentin / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D014746:Vimentin; D002956:Citrulline; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases