Local production of B lymphocyte stimulator protein and APRIL in arthritic joints of patients with inflammatory arthritis

Arthritis Rheum. 2003 Apr;48(4):982-92. doi: 10.1002/art.10860.


Objective: To determine whether synovial fluid (SF) levels and cell-surface expression of B lymphocyte stimulator (BLyS) protein and SF levels of APRIL are elevated in patients with inflammatory arthritis (IA).

Methods: Same-day blood and SF samples from 89 patients with 103 knee effusions (81 knees with IA and 22 with noninflammatory arthritis [NIA]) were evaluated for BLyS protein and APRIL levels by enzyme-linked immunosorbent assay. Blood and SF mononuclear cells were double-stained for surface BLyS protein and surface CD14 (monocyte marker) and were analyzed by flow cytometry. Complete blood cell counts and SF nucleated cell counts were performed by the clinical hematology laboratory.

Results: BLyS protein levels were higher in SF than in corresponding serum samples from both IA and NIA patients. SF BLyS protein levels, but not surface expression of BLyS protein, were disproportionately elevated in IA patients. APRIL levels were higher in SF than in corresponding serum samples from most IA patients but not NIA patients. SF BLyS protein and APRIL levels correlated with each other, and each correlated with SF monocyte, lymphocyte, neutrophil, and total nucleated cell counts. Although SF and serum BLyS protein levels correlated with each other, SF and serum APRIL levels did not, suggesting that SF BLyS protein levels are more dependent upon systemic factors than are SF APRIL levels. Moreover, in 8 patients who underwent sequential arthrocenteses, changes in SF BLyS protein levels did not immutably parallel changes in SF APRIL levels, indicating their differential regulation.

Conclusion: BLyS protein and APRIL are locally produced in inflamed joints. Their respective SF levels are differentially regulated, suggesting that they serve different functions. Together, their local production may foster survival and/or expansion of B cells that produce pathogenic autoantibodies and/or promote local T cell activation and consequent joint destruction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / metabolism*
  • B-Cell Activating Factor
  • Cell Count
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Knee Joint / metabolism*
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / metabolism
  • Neuropeptides / metabolism*
  • Nuclear Proteins / metabolism*
  • Synovial Fluid / cytology
  • Synovial Fluid / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*


  • ANP32B protein, human
  • B-Cell Activating Factor
  • Lipopolysaccharide Receptors
  • Membrane Proteins
  • Neuropeptides
  • Nuclear Proteins
  • TNFSF13B protein, human
  • Tumor Necrosis Factor-alpha