Upregulated baseline plasma CCL19 and CCR7 cell-surface expression on monocytes in early rheumatoid arthritis normalized during treatment and CCL19 correlated with radiographic progression
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Upregulated baseline plasma CCL19 and CCR7 cell-surface expression on monocytes in early rheumatoid arthritis normalized during treatment and CCL19 correlated with radiographic progression. / Ellingsen, T; Hansen, I; Thorsen, Jesper; Møller, B K; Tarp, U; Lottenburger, T; Andersen, L S; Skjødt, H; Pedersen, J K; Lauridsen, U B; Svendsen, A; Lindegaard, H; Jacobsen, S; Østergaard, M; Vestergaard, A; Jurik, A G; Junker, P; Christensen, A F; Hetland, M L; Hørslev-Petersen, K; Stengaard-Pedersen, K.
In: Scandinavian Journal of Rheumatology, Vol. 43, No. 2, 2014, p. 91-100.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Upregulated baseline plasma CCL19 and CCR7 cell-surface expression on monocytes in early rheumatoid arthritis normalized during treatment and CCL19 correlated with radiographic progression
AU - Ellingsen, T
AU - Hansen, I
AU - Thorsen, Jesper
AU - Møller, B K
AU - Tarp, U
AU - Lottenburger, T
AU - Andersen, L S
AU - Skjødt, H
AU - Pedersen, J K
AU - Lauridsen, U B
AU - Svendsen, A
AU - Lindegaard, H
AU - Jacobsen, S
AU - Østergaard, M
AU - Vestergaard, A
AU - Jurik, A G
AU - Junker, P
AU - Christensen, A F
AU - Hetland, M L
AU - Hørslev-Petersen, K
AU - Stengaard-Pedersen, K
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Antibodies, Anti-Idiotypic
KW - Antirheumatic Agents
KW - Arthritis, Rheumatoid
KW - C-Reactive Protein
KW - CD4-Positive T-Lymphocytes
KW - Chemokine CCL19
KW - Cyclosporine
KW - Disease Progression
KW - Drug Therapy, Combination
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Longitudinal Studies
KW - Male
KW - Methotrexate
KW - Middle Aged
KW - Monocytes
KW - Peptides, Cyclic
KW - Receptors, CCR7
KW - Severity of Illness Index
KW - Treatment Outcome
KW - Up-Regulation
U2 - 10.3109/03009742.2013.803149
DO - 10.3109/03009742.2013.803149
M3 - Journal article
C2 - 23980529
VL - 43
SP - 91
EP - 100
JO - Scandinavian Journal of Rheumatology
JF - Scandinavian Journal of Rheumatology
SN - 0300-9742
IS - 2
ER -
ID: 138503083