Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

Page: [316 - 320] Pages: 5

  • * (Excluding Mailing and Handling)

Abstract

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases.

Objectives: In this study, we evaluated the association between serum calprotectin level and severity of RA activity.

Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated.

Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05).

Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

Keywords: CRP, calprotectin, disease activity, ESR, rheumatoid arthritis, RF.

Graphical Abstract

[1]
West S. Clinical overview of rheumatoid arthritislung disease in rheumatoid arthritis. Springer 2018; pp. 1-18.
[http://dx.doi.org/10.1007/978-3-319-68888-6_1]
[2]
Kalappan M, Abubacker NRT, Shetty M, Rajendran K, Rathinam WKM, Karuthodiyil R. Study of extra-articular manifestations and disease severity in patients with rheumatoid arthritis. Int J Adv Med 2017; 3: 53-6.
[3]
Jonsson MK, Sundlisæter NP, Nordal HH, Hammer HB, Aga A-B, van der Heijde D, et al. Response to:‘Calprotectin is not independent from baseline erosion in predicting radiological progression in early rheumatoid arthritis’ by Chevreau et al Ann Rheum Dis 2018. Annrheumdis-2017-212869
[4]
Liao H, Wu J, Kuhn E, et al. Use of mass spectrometry to identify protein biomarkers of disease severity in the synovial fluid and serum of patients with rheumatoid arthritis. Arthritis Rheum 2004; 50(12): 3792-803.
[http://dx.doi.org/10.1002/art.20720] [PMID: 15593230]
[5]
Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Harrison's principles of internal medicine, 19: e2015.
[6]
Nordal HH, Brun JG, Halse A-K, Jonsson R, Fagerhol MK, Hammer HB. The neutrophil protein S100A12 is associated with a comprehensive ultrasonographic synovitis score in a longitudinal study of patients with rheumatoid arthritis treated with adalimumab. BMC Musculoskelet Disord 2014; 15: 335.
[http://dx.doi.org/10.1186/1471-2474-15-335] [PMID: 25282581]
[7]
Turesson C, O’Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis 2003; 62(8): 722-7.
[http://dx.doi.org/10.1136/ard.62.8.722] [PMID: 12860726]
[8]
Turesson C, Jacobsson LT. Epidemiology of extra-articular manifestations in rheumatoid arthritis. Scand J Rheumatol 2004; 33(2): 65-72.
[http://dx.doi.org/10.1080/03009740310004621] [PMID: 15163106]
[9]
Madland TM. Calprotectin (S100A8/A9) and S100A12 in inflammatory arthritis: clinical and epidemiological studies of rheumatoid and psoriatic arthritis 2007.
[10]
García-Arias M, Pascual-Salcedo D, Ramiro S, et al. Calprotectin in rheumatoid arthritis: association with disease activity in a cross-sectional and a longitudinal cohort. Mol Diagn Ther 2013; 17(1): 49-56.
[http://dx.doi.org/10.1007/s40291-013-0016-9] [PMID: 23329363]
[11]
Hammer HB, Ødegard S, Fagerhol MK, et al. Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis. Ann Rheum Dis 2007; 66(8): 1093-7.
[http://dx.doi.org/10.1136/ard.2006.064741] [PMID: 17234650]
[12]
Dale I, Fagerhol MK, Frigård M. Quantitation of a highly immunogenic leukocyte antigen (L1) by radioimmunoassay: methodological evaluation. J Immunol Methods 1983; 65(1-2): 245-55.
[http://dx.doi.org/10.1016/0022-1759(83)90321-6] [PMID: 6418818]
[13]
Foell D, Wittkowski H, Vogl T, Roth J. S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J Leukoc Biol 2007; 81(1): 28-37.
[http://dx.doi.org/10.1189/jlb.0306170] [PMID: 16943388]
[14]
Edwards CJ, Feldman JL, Beech J, et al. Molecular profile of peripheral blood mononuclear cells from patients with rheumatoid arthritis. Mol Med 2007; 13(1-2): 40-58.
[http://dx.doi.org/10.2119/2006-000056.Edwards] [PMID: 17515956]
[15]
Chen Y-S, Yan W, Geczy CL, Brown MA, Thomas R. Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis. Arthritis Res Ther 2009; 11(2): R39.
[http://dx.doi.org/10.1186/ar2645] [PMID: 19284577]
[16]
Andrés Cerezo L, Mann H, Pecha O, 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; 13(4): R122.
[http://dx.doi.org/10.1186/ar3426] [PMID: 21791097]
[17]
Abildtrup M, Kingsley GH, Scott DL. Calprotectin as a biomarker for rheumatoid arthritis: a systematic review. The Journal of rheumatology 2015. jrheum. 140628.
[http://dx.doi.org/10.3899/jrheum.140628] [PMID: 25729036]
[18]
Frosch M, Strey A, Vogl T, et al. Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum 2000; 43(3): 628-37.
[http://dx.doi.org/10.1002/1529-0131(200003)43:3<628:AID-ANR20>3.0.CO;2-X] [PMID: 10728757]
[19]
Hurnakova J, Zavada J, Hanova P, et al. Serum calprotectin (S100A8/9): an independent predictor of ultrasound synovitis in patients with rheumatoid arthritis. Arthritis Res Ther 2015; 17: 252.
[http://dx.doi.org/10.1186/s13075-015-0764-5] [PMID: 26373925]
[20]
Anderson J, Caplan L, Yazdany J, et al. Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice. Arthritis Care Res (Hoboken) 2012; 64(5): 640-7.
[http://dx.doi.org/10.1002/acr.21649] [PMID: 22473918]
[21]
Mansour HE, Abdullrhman MA, Mobasher SA, et al. Serum calprotectin in rheumatoid arthritis: A promising diagnostic marker, how far is it related to activity and sonographic findings? J Med Ultrasound 2017; 25(1): 40-6.
[http://dx.doi.org/10.1016/j.jmu.2016.11.001] [PMID: 30065453]
[22]
Adel N, William M, Swaff R, Hassan S. Serum calprotectin level for diagnosis and detection of disease activity in rheumatoid arthritis. Int J Immunol 2014; 2: 6-10.
[http://dx.doi.org/10.11648/j.iji.20140201.12]
[23]
Hammer HB, Ødegård S, Syversen SW, et al. Calprotectin (a major S100 leucocyte protein) predicts 10-year radiographic progression in patients with rheumatoid arthritis. Ann Rheum Dis 2010; 69(1): 150-4.
[http://dx.doi.org/10.1136/ard.2008.103739] [PMID: 19095696]
[24]
Hammer HB, Fagerhol MK, Wien TN, Kvien TK. 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; 13(5): R178.
[http://dx.doi.org/10.1186/ar3503] [PMID: 22029973]
[25]
Nordal HH, Brokstad KA, Solheim M, Halse A-K, Kvien TK, Hammer HB. 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; 19(1): 3.
[http://dx.doi.org/10.1186/s13075-016-1201-0] [PMID: 28081709]
[26]
Jonsson MK, Sundlisæter NP, Nordal HH, Hammer HB, Aga A-B, Olsen IC, et al. Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis. Annals of the rheumatic diseases 2017. annrheumdis-2017-211695.
[http://dx.doi.org/10.1136/annrheumdis-2017-211695] [PMID: 28814431]
[27]
Brun JG, Jonsson R, Haga HJ. Measurement of plasma calprotectin as an indicator of arthritis and disease activity in patients with inflammatory rheumatic diseases. J Rheumatol 1994; 21(4): 733-8.
[PMID: 8035402]