Calprotectin, a biomarker for neutrophil activation and inflammation, has been shown to have clinical diagnostic value in assessment of disease activity in rheumatoid arthritis (RA), including the potential to monitor the treatment response.
Why does calprotectin levels reflect the joint inflammatory activity directly?
During inflammation, neutrophils migrate to the inflammatory site and secrete large amounts of calprotectin, which act as a soluble proinflammatory mediator1. Calprotectin is released locally at inflammation sites, including inflamed synovium, and enters the systemic circulation where it can be measured. Since calprotectin is released predominantly from locally activated leukocytes at the sites of joint inflammation, it directly reflects joint inflammatory activity2,3.
Can calprotectin in blood monitor disease activity in RA?
Since the concentration of calprotectin reflects the degree of inflammation and correlates with clinical scores4-6, it is a good diagnostic tool and can provide valuable monitoring of the disease activity, treatment response and relapse 3,7,8.
Furthermore, since circulating calprotectin is elevated in active disease and decreases after effective treatment it has shown to be a more sensitive biomarker of disease activity in RA than conventionally used acute-phase proteins8-16.
Calprotectin levels correlate with multiple disease scores and increase with disease severity.
(Figure from Inciarte-Mundo J, et al. Arthritis Care & Research. 2016 (10). Calprotectin serum levels in RA patients according to disease status using the Disease Activity Score in 28 joints (DAS28), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI).)
How does calprotectin compare to other inflammatory markers in RA?
Calprotectin levels correlates with levels of other classically used inflammation markers, like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)17-19. However, calprotectin may be more effective than ESR and CRP to gauge disease activity, as it has been demonstrated that more than 40 % of RA patients have normal ESR or CRP20. Calprotectin can potentially be a useful inflammatory marker for these patients as it has shown diagnostic value in patients with normal/low CRP levels21-23.
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- Ometto F et al. Calprotectin in rheumatic diseases. Exp Biol Med (Maywood). 2017.
- Wang Q et al. The Role of Calprotectin in Rheumatoid Arthritis. J Transl Int Med. 2019.
- Abildtrup M et al. Calprotectin as a biomarker for rheumatoid arthritis: a systematic review. J Rheumatol. 2015.
- Bae SC, Lee YH. Calprotectin levels in rheumatoid arthritis and their correlation with disease activity: a meta-analysis. Postgrad Med. 2017.
- Hammer HB et al. Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis. Ann Rheum Dis. 2007.
- Hurnakova J et al. Relationship between serum calprotectin (S100A8/9) and clinical, laboratory and ultrasound parameters of disease activity in rheumatoid arthritis: A large cohort study. PLoS One. 2017.
- Ramírez J et al. Clinical and sonographic biomarkers of structural damage progression in RA patients in clinical remission: A prospective study with 12 months follow-up. Semin Arthritis Rheum. 2017.
- Nielsen UB et al. Calprotectin in patients with chronic rheumatoid arthritis correlates with disease activity and responsiveness to methotrexate. Scand J Clin Lab Invest. 2018.
- Andrés Cerezo L et al. Decreases in serum levels of S100A8/9 (calprotectin) correlate with improvements in total swollen joint count in patients with recent-onset rheumatoid arthritis. Arthritis Res Ther. 2011.
- Inciarte-Mundo J et al. Serum Calprotectin Versus Acute-Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors [published correction appears in Arthritis Care Res (Hoboken). 2017 Jan;69(1):155]. Arthritis Care Res (Hoboken). 2016.
- Hurnakova J et al. Serum calprotectin (S100A8/9): an independent predictor of ultrasound synovitis in patients with rheumatoid arthritis. Arthritis Res Ther. 2015.
- Inciarte-Mundo J et al. Calprotectin more accurately discriminates the disease status of rheumatoid arthritis patients receiving tocilizumab than acute phase reactants. Rheumatology (Oxford). 2015.
- Hurnakova J et al. Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remission in Patients with Rheumatoid Arthritis in Clinical Remission. PLoS One. 2016.
- Nordal HH et al. Calprotectin (S100A8/A9) has the strongest association with ultrasound-detected synovitis and predicts response to biologic treatment: results from a longitudinal study of patients with established rheumatoid arthritis. Arthritis Res Ther. 2017.
- Jonsson MK, et al. Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis. Ann Rheum Dis. 2017.
- Hammer HB et al. The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab. Arthritis Res Ther. 2011.
- Berntzen HB et al. A longitudinal study of the leukocyte protein L1 as an indicator of disease activity in patients with rheumatoid arthritis. J Rheumatol. 1989.
- Berntzen HB et al. The major leukocyte protein L1 as an indicator of inflammatory joint disease. Scand J Rheumatol Suppl. 1988.
- García-Arias M et al. Calprotectin in rheumatoid arthritis : association with disease activity in a cross-sectional and a longitudinal cohort. Mol Diagn Ther. 2013.
- Pincus T and Sokka T. Laboratory tests to assess patients with rheumatoid arthritis: advantages and limitations. Rheum Dis Clin North Am. 2009.
- Hurnakova J et al. Serum calprotectin may reflect inflammatory activity in patients with active rheumatoid arthritis despite normal to low C-reactive protein. Clin Rheumatol. 2018.
- Jarlborg M et al. Serum calprotectin: a promising biomarker in rheumatoid arthritis and axial spondyloarthritis. Arthritis Res Ther. 2020.
- Wang Y and Liang Y. Clinical significance of serum calprotectin level for the disease activity in active rheumatoid arthritis with normal C-reactive protein. Int J Clin Exp Pathol. 2019.