title: Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis: association with disease activity but different response patterns to synthetic and biologic DMARDs.
abstract: 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=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.
authors.affiliation: Department of Biomedicine, Aarhus University; and Department of Rheumatology, Aarhus University Hospital, Denmark.
authors.forename: Stinne Ravn
authors.initials: SR
authors.lastname: Greisen
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Stengaard-Pedersen
authors.affiliation: 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.
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.affiliation: King Christian 10th Hospital for the Rheumatic Diseases, and University of Southern Denmark, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Hørslev-Petersen
authors.affiliation: Department of Rheumatology, Odense University Hospital, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Junker
authors.affiliation: 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.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Department of Biomedicine, and Department of Clinical Medicine, Aarhus University, Denmark.
authors.forename: Malene
authors.initials: M
authors.lastname: Hvid
authors.affiliation: Department of Biomedicine, Aarhus University; Department of Rheumatology, Aarhus University Hospital; and Department of Clinical Medicine, Aarhus University, Denmark.
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
mesh_terms: D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D062072:Patient Acuity; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000097:blood*; D051116:Receptors, Scavenger / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000098902:CD163 Antigen
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018501:Antirheumatic Agents; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D008727:Methotrexate