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

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.

• Authors: T Ellingsen, I Hansen, J Thorsen, B K Møller, U Tarp, T Lottenburger, L S Andersen, H Skjødt, J K Pedersen, U B Lauridsen, A Svendsen, H Lindegaard, S Jacobsen, M Østergaard, A Vestergaard, A G Jurik, P Junker, A F Christensen, M L Hetland, K Hørslev-Petersen, K Stengaard-Pedersen
• Journal: Scandinavian journal of rheumatology (Scand J Rheumatol) Vol. 43 Issue 2 Pg. 91-100 ( 2014) ISSN: 1502-7732 [Electronic] England
• PMID: 23980529 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• Antirheumatic Agents
• CCL19 protein, human
• CCR7 protein, human
• Chemokine CCL19
• Peptides, Cyclic
• Receptors, CCR7
• cyclic citrullinated peptide
• Cyclosporine
• C-Reactive Protein
• Methotrexate

Topics

• Adult
• Aged
• Antibodies, Anti-Idiotypic (blood)
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (blood, diagnostic imaging, drug therapy)
• C-Reactive Protein (metabolism)
• CD4-Positive T-Lymphocytes (metabolism, pathology)
• Chemokine CCL19 (blood)
• Cyclosporine (therapeutic use)
• Disease Progression
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Longitudinal Studies
• Male
• Methotrexate (therapeutic use)
• Middle Aged
• Monocytes (metabolism, pathology)
• Peptides, Cyclic (immunology)
• Radiography
• Receptors, CCR7 (blood)
• Severity of Illness Index
• Treatment Outcome
• Up-Regulation