Kristian Stengaard-Pedersen

Upregulated baseline plasma CCL19 and CCR7 cell-surface expression on monocytes in early rheumatoid arthritis normalized during treatment and CCL19 correlated with radiographic progression

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • T Ellingsen, Denmark
  • I Hansen, Denmark
  • J Thorsen, Denmark
  • B K Møller
  • U Tarp, Denmark
  • T Lottenburger
  • ,
  • L S Andersen, King Christian X Rheumatism Hospital, University of Southern Denmark, Graasten, Denmark
  • ,
  • H Skjødt
  • ,
  • J K Pedersen
  • U B Lauridsen
  • ,
  • Anders Jørgen Svendsen, Department of Rheumatology, Southern University Hospital of Denmark, Odense, Denmark, Denmark
  • H Lindegaard, Department of Rheumatology, Southern University Hospital of Denmark, Odense, Denmark, Denmark
  • S Jacobsen, Department of Rheumatology Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  • ,
  • M Østergaard, Department of Rheumatology, Copenhagen University Hospital at Glostrup, Glostrup, Denmark, Denmark
  • A Vestergaard, Department of Rheumatology, Copenhagen University Hospital at Glostrup, Glostrup, Denmark, Denmark
  • A G Jurik
  • P Junker
  • ,
  • A F Christensen, Department of Rheumatology, Southern University Hospital of Denmark, Odense, Denmark, Denmark
  • M L Hetland
  • ,
  • K Hørslev-Petersen
  • ,
  • K Stengaard-Pedersen

OBJECTIVES: 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.

METHOD: 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.

Original languageEnglish
JournalScandinavian Journal of Rheumatology
Volume43
Issue2
Pages (from-to)91-100
Number of pages10
ISSN0300-9742
DOIs
Publication statusPublished - 2014

    Research areas

  • Adult, Aged, Antibodies, Anti-Idiotypic, Antirheumatic Agents, Arthritis, Rheumatoid, C-Reactive Protein, CD4-Positive T-Lymphocytes, Chemokine CCL19, Cyclosporine, Disease Progression, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Methotrexate, Middle Aged, Monocytes, Peptides, Cyclic, Receptors, CCR7, Severity of Illness Index, Treatment Outcome, Up-Regulation

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