title: Upregulated baseline plasma CCL19 and CCR7 cell-surface expression on monocytes in early rheumatoid arthritis normalized during treatment and CCL19 correlated with radiographic progression.
abstract: OBJECTIVE
  The aim of this study was to measure, in early rheumatoid arthritis (RA) patients, the concentration of CC-chemokine ligand 19 (CCL19) in plasma and the cell-surface expression of CC-chemokine receptor 7 (CCR7) on circulating monocytes and CD4+ T lymphocytes and to analyse correlations with disease activity and 5-year radiographic progression.
  
  
  METHODS
  In disease-modifying anti-rheumatic drug (DMARD)-naïve RA patients (disease duration < 6 months), we measured plasma CCL19 by enzyme-linked immunosorbent assay (ELISA) (n = 160) and CCR7 cell-surface expression on monocytes and CD4+ T lymphocytes by flow cytometry (n = 40) at baseline and after 1 year of treatment with methotrexate (MTX) or methotrexate+cyclosporin A (MTX/CyA). Radiographic progression was scored by the van der Heijde-modified Total Sharp Score (TSS) from 0 to 5 years.
  
  
  RESULTS
  Increased baseline CCL19 (median 85 pg/mL, range 31-1008 pg/mL, p = 0.01) decreased after 1 year (median 31 pg/mL, range 31-1030 pg/mL, p < 0.001) and 5 years (median 31 pg/mL, range 31-247 pg/mL, p < 0.001) to a level below the controls (n = 45) (median 60 pg/mL, range 31-152 pg/mL). Baseline plasma CCL19 levels [p = 0.011, 95% confidence interval (CI) 0.0030-0.0176], anti-cyclic citrullinated peptide (anti-CCP) antibody status (p = 0.002, 95% CI 0.61-2.38), and TSS > 0 at baseline (p < 0.001, 95% CI 1.21-3.16) were independent predictors of 5-year radiographic progression evaluated by multiple logistic regression in contrast to never smoked, C-reactive protein (CRP), gender, age, number of tender (NTJ) and swollen joints (NSJ), and 28-joint Disease Activity Score (DAS28). Increased CCR7 expression on monocytes (p = 0.008) correlated to CRP (p = 0.006, r = 0.52) and normalized (n = 15) after 1 year (p = 0.02).
  
  
  CONCLUSIONS
  In DMARD-naïve RA patients, CCL19 plasma level and CCR7 surface expression on monocytes were upregulated and normalized after 1 year of treatment. Increased baseline plasma CCL19 level, anti-CCP antibody status, and TSS > 0 at baseline correlated independently with 5-year radiographic progression.
authors: Department of Rheumatology, Aarhus University Hospital , Aarhus , Denmark.
authors: T
authors: T
authors: Ellingsen
authors: I
authors: I
authors: Hansen
authors: J
authors: J
authors: Thorsen
authors: B K
authors: BK
authors: Møller
authors: U
authors: U
authors: Tarp
authors: T
authors: T
authors: Lottenburger
authors: L S
authors: LS
authors: Andersen
authors: H
authors: H
authors: Skjødt
authors: J K
authors: JK
authors: Pedersen
authors: U B
authors: UB
authors: Lauridsen
authors: A
authors: A
authors: Svendsen
authors: H
authors: H
authors: Lindegaard
authors: S
authors: S
authors: Jacobsen
authors: M
authors: M
authors: Østergaard
authors: A
authors: A
authors: Vestergaard
authors: A G
authors: AG
authors: Jurik
authors: P
authors: P
authors: Junker
authors: A F
authors: AF
authors: Christensen
authors: M L
authors: ML
authors: Hetland
authors: K
authors: K
authors: Hørslev-Petersen
authors: K
authors: K
authors: Stengaard-Pedersen
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D054415:Chemokine CCL19 / Q000097:blood*; D016572:Cyclosporine / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D010456:Peptides, Cyclic / Q000276:immunology; D011859:Radiography; D054400:Receptors, CCR7 / Q000097:blood*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000888:Antibodies, Anti-Idiotypic; D018501:Antirheumatic Agents; C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D010456:Peptides, Cyclic; D054400:Receptors, CCR7; C487763:cyclic citrullinated peptide; D016572:Cyclosporine; D002097:C-Reactive Protein; D008727:Methotrexate