title: Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers.
abstract: BACKGROUND
  The aim of this study was to identify and characterize subclinical synovitis in patients with rheumatoid arthritis (RA) in clinical remission using power Doppler ultrasound (PDUS) and serum levels of biomarkers of inflammation and/or angiogenesis.
  
  
  METHODS
  We selected patients with RA in clinical remission defined as a Disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for more than six months tested by two independent rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. PDUS of knees and hands was performed by a sonographer. Synovial hypertrophy (SH) and PDUS signal were scored (grades 0 to 3). SH ≥2 and a PDUS signal was classified as active synovitis. Serum levels of biomarkers of inflammation/angiogenesis were determined by Quantibody Human Array.
  
  
  RESULTS
  This study included 55 patients, of whom 25 (45.4%) met criteria for ultrasound-defined active synovitis. Patients with active synovitis had higher DAS28-C reactive protein (P = 0.023), DAS28-ESR (P = 0.06), simplified disease activity score, SDAI (P = 0.064), and only 12% were taking oral glucocorticoids (≤5 mg/day) compared with 40% of patients without active synovitis (P = 0.044). Patients with synovitis also had significantly higher serum levels of the angiogenic biomarkers angiopoietin-2 (P = 0.038), vascular endothelial growth factor-D (P = 0.018), placental growth factor (P = 0.043), stromal cell-derived factor-1 (P = 0.035), matrix metallopeptidase-2 (P = 0.027) and basic fibroblast growth factor (bFGF) (P = 0.007), but not of pro-inflammatory cytokines.
  
  
  CONCLUSIONS
  Nearly half of the patients with RA in clinical remission had ultrasound-defined active synovitis, higher disease activity and less frequent oral glucocorticoid consumption than patients without active synovitis. This clinical situation was associated with a specific biological profile characterized by an excess of angiogenic mediators rather than persistent proinflammatory cytokine responses.
authors.forename: Julio
authors.initials: J
authors.lastname: Ramírez
authors.forename: Virginia
authors.initials: V
authors.lastname: Ruíz-Esquide
authors.forename: Isaac
authors.initials: I
authors.lastname: Pomés
authors.forename: Raquel
authors.initials: R
authors.lastname: Celis
authors.forename: Andrea
authors.initials: A
authors.lastname: Cuervo
authors.forename: Ma Victoria
authors.initials: MV
authors.lastname: Hernández
authors.forename: Jaume
authors.initials: J
authors.lastname: Pomés
authors.forename: José L
authors.initials: JL
authors.lastname: Pablos
authors.forename: Raimon
authors.initials: R
authors.lastname: Sanmartí
authors.forename: Juan D
authors.initials: JD
authors.lastname: Cañete
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood*; D012074:Remission Induction; D012680:Sensitivity and Specificity; D013585:Synovitis / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D018608:Ultrasonography, Doppler
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers