Cathepsin S and cathepsin L in serum and synovial fluid in rheumatoid arthritis with and without autoantibodies

Rheumatology (Oxford). 2015 Oct;54(10):1923-8. doi: 10.1093/rheumatology/keu486. Epub 2015 Jun 8.


Objectives: Cathepsin S and cathepsin L are endosomal proteolytic enzymes involved in the degradation of extracellular matrixes, angiogenesis and antigen presentation. Cathepsins could thus play several roles in the disease process of RA. The aim of this study was to examine differences in cathepsin S and cathepsin L levels in serum and SF of RA patients with and without ACPA and RF.

Methods: In this study 121 patients with RA and clinical signs of knee synovitis were recruited. Patient characteristics were collected and matched samples of serum and SF were analysed for cathepsin S, cathepsin L, ACPA, IgA and IgM RF, CRP and MMP3.

Results: SF levels of cathepsin L, cathepsin S and MMP3 were significantly higher than in serum. Serum levels of both cathepsins were significantly higher in patients with ACPA, IgM-RF and IgA-RF compared with patients without these antibodies. SF levels of both cathepsins correlated with DAS28 and CRP in ACPA- and RF-positive but not in seronegative patients.

Conclusion: The differences in cathepsin S and cathepsin L between RA patients with and without autoantibodies indicate that these cathepsins have a specific role in the disease process of seropositive RA. In this phenotype, cathepsin serum levels may reflect the autoimmune activity, whereas the levels in SF may reflect the local inflammatory and matrix degrading process in the joint.

Keywords: ACPA; cathepsin L; cathepsin S; rheumatoid arthritis; rheumatoid factor.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism*
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Cathepsin L / analysis*
  • Cathepsin L / blood*
  • Cathepsins / analysis*
  • Cathepsins / blood*
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin M / blood
  • Male
  • Matrix Metalloproteinase 3 / blood
  • Middle Aged
  • Peptides, Cyclic / immunology
  • Phenotype
  • Rheumatoid Factor / blood
  • Severity of Illness Index
  • Synovial Fluid / chemistry*


  • Autoantibodies
  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin M
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • C-Reactive Protein
  • Rheumatoid Factor
  • Cathepsins
  • Cathepsin L
  • cathepsin S
  • Matrix Metalloproteinase 3