Calprotectin in rheumatoid arthritis : association with disease activity in a cross-sectional and a longitudinal cohort

Mol Diagn Ther. 2013 Feb;17(1):49-56. doi: 10.1007/s40291-013-0016-9.


Background: Calprotectin is potentially a more sensitive biomarker of disease activity in rheumatoid arthritis (RA) than conventional acute-phase proteins such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) because it directly reflects inflammation in the synovium and synovial fluid rather than systemic inflammatory activity.

Objective: The aim of this study was to evaluate relationships between serum calprotectin levels, disease activity, and response to treatment. Calprotectin was also investigated as a predictive marker of clinical response.

Methods: This observational study included selected cohorts of patients with RA treated at La Paz University Hospital, Madrid, Spain. Associations between serum calprotectin levels and clinical and laboratory parameters were analyzed in a cross-sectional cohort of 60 patients with varying disease activity, and changes in calprotectin levels in response to treatment with infliximab were analyzed at baseline and after 3 and 6 months of treatment in a longitudinal cohort of 20 patients with very active disease.

Results: In the cross-sectional cohort, calprotectin levels correlated with rheumatoid factor levels (r = 0.25; p < 0.05) but not with titers of antibodies to cyclic citrullinated peptide. Significant correlations were also observed between calprotectin levels and the 28 swollen joint count (28-SJC), Disease Activity Score based on a 28-joint count (DAS28), Simplified Disease Activity Index (SDAI), ESR, and CRP levels. In the longitudinal cohort, calprotectin levels at baseline were not predictive of response to treatment but significantly decreased during treatment in responders (p < 0.0001).

Conclusion: Calprotectin levels strongly correlate with clinical and laboratory assessments of joint inflammation and also decrease in response to treatment, indicating that calprotectin is a promising marker for assessment and monitoring of disease activity in patients with RA. Investigations are required to further evaluate its diagnostic, prognostic, and therapeutic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnosis*
  • Biomarkers / blood
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Cross-Sectional Studies
  • Endpoint Determination
  • Female
  • Humans
  • Infliximab
  • Leukocyte L1 Antigen Complex / blood*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Peptides, Cyclic / metabolism
  • Prognosis
  • Spain
  • Synovial Fluid / metabolism
  • Synovial Membrane / metabolism


  • Acute-Phase Proteins
  • Antibodies, Monoclonal
  • Biomarkers
  • Leukocyte L1 Antigen Complex
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • C-Reactive Protein
  • Infliximab