Decoy receptor 3 suppresses B cell functions and has a negative correlation with disease activity in rheumatoid arthritis

Clin Exp Rheumatol. 2014 Sep-Oct;32(5):715-23. Epub 2014 Aug 1.

Abstract

Objectives: The decoy receptor 3 (DcR3) is a member of the tumour necrosis factor (TNF) receptor superfamily and may regulate inflammation. The aim of this study was to investigate the role of DcR3 in B cell functions and its correlation to disease activity in patients with rheumatoid arthritis (RA).

Methods: The concentrations of DcR3 and TNF-α were measured by ELISA. B cell proliferation was assessed by quantification of 3H-thymidine uptake. Staphylococcus aureus Cowan (SAC) strain were used to stimulate B cell proliferation and TNF-α production.

Results: Compared to the osteoarthritis (OA) patients, the RA group had higher synovial DcR3 levels (3273.6±1623.2 vs. 1594.8±1190.0 pg/ml, p=0.003), which were negatively correlated with the serum erythrocyte sedimentation rate and Disease Activity Score using 28 joint counts (DAS28) scores (r=-0.560, p=0.002; r=-0.579, p<0.001, respectively). Although the RA B cells have more active characteristics, B cell proliferation induced by SAC was successfully suppressed by recombinant DcR3.Fc fusion protein with an average inhibition of 44.8%. Moreover, DcR3.Fc fusion protein was found to suppress SAC-induced TNF-α production by B cells in 8 RA patients (average inhibition 47.0%).

Conclusions: The results of our study indicated that the inhibition of B cell functions by DcR3 may partially explain the negative correlation between DcR3 level and disease activity in RA patients. Our findings imply that DcR3 may be used as a biomarker for disease activity and a potential therapeutic agent in the treatment of RA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / diagnosis
  • Osteoarthritis, Knee / immunology
  • Osteoarthritis, Knee / metabolism
  • Receptors, Tumor Necrosis Factor, Member 6b / metabolism*
  • Severity of Illness Index
  • Signal Transduction
  • Synovial Fluid / immunology
  • Synovial Fluid / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Biomarkers
  • Receptors, Tumor Necrosis Factor, Member 6b
  • TNFRSF6B protein, human
  • Tumor Necrosis Factor-alpha