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

1, 2, 3, 4, 5, 6, 7, 8, 9

  1. Department of Biomedicine, Aarhus University; and Department of Rheumatology, Aarhus University Hospital, Denmark.
  2. Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.
  3. Department of Rheumatology, Aarhus University Hospital, Denmark
  4. Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases, Glostrup Hospital; and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  5. King Christian 10th Hospital for the Rheumatic Diseases, and University of Southern Denmark, Denmark.
  6. Department of Rheumatology, Odense University Hospital, Denmark.
  7. Copenhagen Centre for Arthritis Research, Centre for Rheumatology and Spine Diseases, Glostrup Hospital; and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  8. Department of Biomedicine, and Department of Clinical Medicine, Aarhus University, Denmark.
  9. Department of Biomedicine, Aarhus University; Department of Rheumatology, Aarhus University Hospital; and Department of Clinical Medicine, Aarhus University, Denmark.

Department of Biomedicine, Aarhus University, Denmark and Department of Rheumatology, Aarhus University Hospital, Denmark

CER8105 Submission on line
2015 Vol.33, N°4 - PI 0498, PF 0502
Full Papers

Rheumatology Article

 

Abstract

OBJECTIVES:
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=0.16-0.28, p<0.05). In the DMARD+PLA group baseline sCD163 also correlated with CRP during the follow-up period.
CONCLUSIONS:
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.

PMID: 25962601 [PubMed]

Received: 11/11/2014 - Accepted : 19/02/2015 - In Press: 11/05/2015 - Published: 20/07/2015