title: Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs.
abstract: BACKGROUND
  Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA.
  
  
  METHODS
  The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months.
  
  
  RESULTS
  Baseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01).
  
  
  CONCLUSIONS
  CXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.
authors.affiliation: Division and Laboratory of Rheumatology, University of Pavia School of Medicine, IRCCS Policlinico San Matteo Foundation, Piazzale Golgi 2, 27100 Pavia, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bugatti
authors.forename: Antonio
authors.initials: A
authors.lastname: Manzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Benaglio
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Barbara
authors.initials: B
authors.lastname: Vitolo
authors.forename: Monica
authors.initials: M
authors.lastname: Todoerti
authors.forename: Garifallia
authors.initials: G
authors.lastname: Sakellariou
authors.forename: Carlomaurizio
authors.initials: C
authors.lastname: Montecucco
authors.forename: Roberto
authors.initials: R
authors.lastname: Caporali
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood*; D054382:Chemokine CXCL13 / Q000097:blood*; D005260:Female; D006801:Humans; D007596:Joints / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D013585:Synovitis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D018615:Ultrasonography, Doppler, Color
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13