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

T Ellingsen, I Hansen, J Thorsen, B K Møller, U Tarp, T Lottenburger, Lis Smedegaard Andersen, H Skjødt, J K Pedersen, U B Lauridsen, Anders Jørgen Svendsen, H Lindegaard, S Jacobsen, M Østergaard, A Vestergaard, A G Jurik, P Junker, A F Christensen, M L Hetland, K Hørslev-PetersenK Stengaard-Pedersen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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
Issue number2
Pages (from-to)91-100
Number of pages10
ISSN0300-9742
DOIs
Publication statusPublished - 2014

Keywords

  • 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

Fingerprint

Dive into the research topics of 'Upregulated baseline plasma CCL19 and CCR7 cell-surface expression on monocytes in early rheumatoid arthritis normalized during treatment and CCL19 correlated with radiographic progression'. Together they form a unique fingerprint.

Cite this