Ellingsen, T4; Hansen, I6; Thorsen, Jesper4; Møller, B K4; Tarp, U4; Lottenburger, T4; Andersen, L S4; Skjødt, H4; Pedersen, J K4; Lauridsen, U B4; Svendsen, A4; Lindegaard, H4; Jacobsen, S7; Østergaard, M4; Vestergaard, A4; Jurik, A G4; Junker, P4; Christensen, A F8; Hetland, M L9; Hørslev-Petersen, K4; Stengaard-Pedersen, K4
1 Functional Genomics, Department of Biology, Faculty of Science, Københavns Universitet2 Natural Products and Peptides, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet3 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet6 Functional Genomics, Department of Biology, Faculty of Science, Københavns Universitet7 Natural Products and Peptides, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Københavns Universitet8 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet9 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
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.
Scandinavian Journal of Rheumatology, 2014, Vol 43, Issue 2, p. 91-100