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

被引:33
作者
Ellingsen, T. [1 ]
Hansen, I. [1 ]
Thorsen, J. [2 ]
Moller, B. K. [2 ]
Tarp, U. [1 ]
Lottenburger, T. [3 ]
Andersen, L. S. [4 ]
Skjodt, H.
Pedersen, J. K. [4 ]
Lauridsen, U. B. [5 ]
Svendsen, A. [3 ]
Lindegaard, H. [3 ]
Jacobsen, S. [6 ]
Ostergaard, M. [5 ]
Vestergaard, A. [5 ]
Jurik, A. G. [7 ]
Junker, P. [3 ]
Christensen, A. F. [3 ]
Hetland, M. L. [5 ]
Horslev-Petersen, K. [4 ]
Stengaard-Pedersen, K. [1 ]
机构
[1] Aarhus Univ Hosp, Dept Rheumatol, DK-8000 Aarhus C, Denmark
[2] Aarhus Univ Hosp, Dept Clin Immunol, Skejby, Denmark
[3] Southern Univ Hosp Denmark, Dept Rheumatol, Odense, Denmark
[4] Univ So Denmark, King Christian X Rheumatism Hosp, Grasten, Denmark
[5] Copenhagen Univ Hosp, Dept Rheumatol, Glostrup, Denmark
[6] Copenhagen Univ Hosp, Rigshosp, Dept Rheumatol, Copenhagen, Denmark
[7] Aarhus Univ Hosp, Dept Radiol, DK-8000 Aarhus C, Denmark
关键词
CHEMOKINE RECEPTOR EXPRESSION; JOINT DAMAGE; PROGNOSTIC-FACTORS; RADIOLOGICAL PROGRESSION; COMBINATION THERAPY; CIGARETTE-SMOKING; DOUBLE-BLIND; BONE EDEMA; ANTI-CCP; 5-YEAR;
D O I
10.3109/03009742.2013.803149
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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)-naive 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 (Cl) 0.0030-0.0176], anti-cyclic citrullinated peptide (anti-CCP) antibody status (p = 0.002,95% CI 0.61-2.38), and TSS > Oat 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-naive RA patients, CCL19 plasma level and CCR7 surface expression on monocytes were upregulated and naunalized 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.
引用
收藏
页码:91 / 100
页数:10
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