Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis: association with disease activity but different response patterns to synthetic and biologic DMARDs

TY - JOUR

T1 - Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis

T2 - association with disease activity but different response patterns to synthetic and biologic DMARDs

AU - Greisen, Stinne Ravn

AU - Møller, Holger Jon

AU - Stengaard-Pedersen, Kristian

AU - Hetland, Merete Lund

AU - Hørslev-Petersen, Kim

AU - Junker, Peter

AU - Østergaard, Mikkel

AU - Hvid, Malene

AU - Deleuran, Bent

PY - 2015

Y1 - 2015

N2 - Objective Rheumatoid arthritis (RA) is a chronic autoimmune disease where TNF-α is a central mediator of inflammation, and is cleaved from the cell surface by TACE/ADAM17. This metalloproteinase is also responsible for the release of soluble (s) CD163. Soluble CD163 reflects macrophage activation. In RA, sCD163 has been suggested as a marker of disease activity and progression. Our aim is to investigate sCD163 levels in early RA patients. Methods Soluble CD163 was measured by ELISA from 150 RA plasma samples from the OPERA trial. Averaged disease duration was three months, prior to randomisation with methotrexate (MTX) and adalimumab (DMARD+ADA) or MTX and placebo (DMARD+PLA). Soluble CD163 levels were evaluated in relation to clinical disease parameters. Results Plasma sCD163 at baseline was 2.39 mg/l (1.74 mg/l-3.18 mg/l), mean (95% CI), vs healthy controls: 1.63 mg/l (1.54 mg/l - 1.73 mg/l), (p<0.001). After three months of treatment sCD163 levels decreased significantly (average 23.5%) in both treatment groups. Significant incremental sCD163 levels followed withdrawal of ADA after 12 months of treatment. Baseline sCD163 correlated with CRP and all investigated disease activity markers (ρ{variant}=0.16-0.28, p<0.05). In the DMARD+PLA group baseline sCD163 also correlated with CRP during the follow-up period. Conclusion Soluble CD163 correlated with disease activity markers in early RA before treatment. Plasma sCD163 may add to currently available disease measures by specifically reflecting changes in macrophage activity as evidenced by increasing levels following anti-TNF withdrawal, despite maintenance of a stable clinical condition achieved by conventional remedies. It remains to be determined whether sCD163 is an early predictor of disease flare.

AB - Objective Rheumatoid arthritis (RA) is a chronic autoimmune disease where TNF-α is a central mediator of inflammation, and is cleaved from the cell surface by TACE/ADAM17. This metalloproteinase is also responsible for the release of soluble (s) CD163. Soluble CD163 reflects macrophage activation. In RA, sCD163 has been suggested as a marker of disease activity and progression. Our aim is to investigate sCD163 levels in early RA patients. Methods Soluble CD163 was measured by ELISA from 150 RA plasma samples from the OPERA trial. Averaged disease duration was three months, prior to randomisation with methotrexate (MTX) and adalimumab (DMARD+ADA) or MTX and placebo (DMARD+PLA). Soluble CD163 levels were evaluated in relation to clinical disease parameters. Results Plasma sCD163 at baseline was 2.39 mg/l (1.74 mg/l-3.18 mg/l), mean (95% CI), vs healthy controls: 1.63 mg/l (1.54 mg/l - 1.73 mg/l), (p<0.001). After three months of treatment sCD163 levels decreased significantly (average 23.5%) in both treatment groups. Significant incremental sCD163 levels followed withdrawal of ADA after 12 months of treatment. Baseline sCD163 correlated with CRP and all investigated disease activity markers (ρ{variant}=0.16-0.28, p<0.05). In the DMARD+PLA group baseline sCD163 also correlated with CRP during the follow-up period. Conclusion Soluble CD163 correlated with disease activity markers in early RA before treatment. Plasma sCD163 may add to currently available disease measures by specifically reflecting changes in macrophage activity as evidenced by increasing levels following anti-TNF withdrawal, despite maintenance of a stable clinical condition achieved by conventional remedies. It remains to be determined whether sCD163 is an early predictor of disease flare.

KW - Adalimumab

KW - Antibodies, Monoclonal, Humanized

KW - Antigens, CD

KW - Antigens, Differentiation, Myelomonocytic

KW - Antirheumatic Agents

KW - Arthritis, Rheumatoid

KW - Biomarkers

KW - Disease Progression

KW - Early Diagnosis

KW - Female

KW - Humans

KW - Macrophage Activation

KW - Male

KW - Methotrexate

KW - Middle Aged

KW - Patient Acuity

KW - Predictive Value of Tests

KW - Receptors, Cell Surface

KW - Receptors, Scavenger

KW - Tumor Necrosis Factor-alpha

M3 - Journal article

C2 - 25962601

SN - 0392-856X

VL - 33

SP - 498

EP - 502

JO - Clinical and Experimental Rheumatology

JF - Clinical and Experimental Rheumatology

IS - 4

ER -