title: CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic 'window of opportunity'.
abstract: BACKGROUND
  A key phenomenon in rheumatoid arthritis is the formation of lymphoid follicles in the inflamed synovial membrane. C-X-C motif chemokine 13 (CXCL13) is central in this process as it attracts C-X-C chemokine receptor type 5 (CXCR5)-expressing B cells and T follicular helper cells to the follicle. We here examine the role of CXCL13 and its association with disease in patients with treatment-naïve early rheumatoid arthritis.
  
  
  METHODS
  Plasma samples from patients in the OPERA trial were examined for CXCL13 at treatment initiation and after 6 months of treatment with either methotrexate plus placebo (DMARD) (n = 37) or methotrexate plus adalimumab (DMARD + ADA) (n = 39). Treatment outcome was evaluated after 1 and 2 years. CXCL13 plasma levels in healthy volunteers (n = 38) were also examined.
  
  
  RESULTS
  Baseline CXCL13 plasma levels were increased in early rheumatoid arthritis patients in comparison with healthy volunteers. Also, plasma CXCL13 correlated positively with disease activity parameters; swollen joint count 28 (rho = 0.34) and 40 (rho = 0.39), visual analog score (rho = 0.38) and simplified disease activity index (rho = 0.25) (all P <0.05). CXCL13 levels decreased a significantly twofold more in the DMARD + ADA group than in the DMARD group. Baseline CXCL13 plasma levels in the DMARD group correlated inversely with disease activity parameters; disease activity score in 28 joints, four variables, C-reactive protein based (DAS28CRP) (rho = 0.58, P < 0.05) at 12 months. High baseline CXCL13 was associated with remission (DAS28CRP less than 2.6) after 2 years.
  
  
  CONCLUSIONS
  In treatment-naïve early rheumatoid arthritis patients, plasma CXCL13 levels were associated with joint inflammation. Furthermore, patients with high baseline plasma CXCL13 levels had an improved chance of remission after 2 years. We propose that high CXCL13 concentrations indicate recent onset of inflammation that may respond better to early aggressive treatment. Thus, high levels of CXCL13 could reflect the 'the window of opportunity' for optimal treatment effect.
  
  
  BACKGROUND
  Clinicaltrial.gov NCT00660647. Registered 10 April 2008.
authors.forename: Stinne Ravn
authors.initials: SR
authors.lastname: Greisen
authors.forename: Karen Kræmmer
authors.initials: KK
authors.lastname: Schelde
authors.forename: Tue Kruse
authors.initials: TK
authors.lastname: Rasmussen
authors.forename: Tue Wenzel
authors.initials: TW
authors.lastname: Kragstrup
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
authors.forename: Malene
authors.initials: M
authors.lastname: Hvid
mesh_terms: D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D054382:Chemokine CXCL13 / Q000097:blood*; D004359:Drug Therapy, Combination; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D000068879:Adalimumab; D008727:Methotrexate