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Egyptian Rheumatology and Rehabilitation
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Potential role of calprotectin as a monitoring biomarker for clinical and sonographic activity and treatment outcome in recent-onset rheumatoid arthritis

Egyptian Rheumatology and Rehabilitation volume 43, pages 143–149 (2016)Cite this article

Abstract

Background

Calprotectin is a protein released during the activation and turnover of leukocytes. It can be used as a biomarker of inflammatory diseases such as rheumatoid arthritis (RA).

Aim

The current study aimed to measure the serum level of calprotectin in RA patients, recently diagnosed and after initiation of treatment, to determine its association with clinical disease, synovial inflammation determined by Ultrasound (US), and its relation to therapy when compared with other inflammatory markers.

Patients and methods

A total of 32 patients with recent RA and 20 healthy individuals were assessed for serum calprotectin level (enzyme-linked immunosorbent assay). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were also measured in patients who were reassessed 4 months after initiation of therapy. Disease activity was evaluated by the disease activity score of 28 joints (DAS28), and US assessment was performed.

Results

The mean level of serum calprotectin was significantly higher (P<0.001) than that of controls. At baseline, there were significant (P<0.001) correlations of calprotectin serum level with DAS28, ESR, CRP, grayscale, and power Doppler (PD) synovitis scores. After therapy, all except DAS28 and ESR significantly correlated with calprotectin serum level. Calprotectin was shown to be better (P=0.001) than CRP (P=0.922) and ESR (P=0.104, r2=0.495) in predicting power Doppler synovitis score. Calprotectin results showed higher sensitivity in predicting disease activity at the stage of active inflammation.

Conclusion

Serum calprotectin level is strongly associated with clinical, laboratory, and US parameters of inflammation in recent-onset RA. Calprotectin is a confident biomarker for monitoring the treatment outcome in RA patients.

References

  1. Kitas GD, Gabriel SE. Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives. Ann Rheum Dis 2011;70:8–14.

    Article  PubMed  Google Scholar 

  2. Van LeeuwenMA, Westra J, Limburg PC, van Riel PL, van Rijswijk MH. Clinical significance of interleukin-6 measurement in early rheumatoid arthritis: relation with laboratory and clinical variables and radiological progression in a three year prospective study. Ann Rheum Dis 1995;54:674–677.

    Article  Google Scholar 

  3. Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum 2004;50:3762–3771.

    Article  CAS  PubMed  Google Scholar 

  4. Odink K, Cerletti N, Bruggen J, Clerc RG, Tarcsay L, Zwadlo G, et al. Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis. Nature 1987;330:80–82.

    Article  CAS  PubMed  Google Scholar 

  5. Dale I, Fagerhol MK, Naesgaard I. Purification and partial characterization of a highly immunogenic human leukocyte protein, the L1 antigen. Eur J Biochem 1983;134:1–6.

    Article  CAS  PubMed  Google Scholar 

  6. Hetey L, Doring E, Penke B. Influence of cholecystokinin on the synaptosomal dopamine uptake in the nucleus accumbens of rats. Neurochem Int 1987;10:525–528.

    Article  CAS  PubMed  Google Scholar 

  7. Johne B, Fagerhol MK, Lyberg T, Prydz H, Brandtzaeg P, Naess-Andresen CF, et al. Functional and clinical aspects of the myelomonocyte protein calprotectin. Mol Pathol 1997;50:113–123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Berntzen HB, Fagerhol MK, Ostensen M, Mowinckel P, Hoyeraal HM. The L1 protein as a new indicator of inflammatory activity in patients with juvenile rheumatoid arthritis. J Rheumatol 1991;18:133–138.

    CAS  PubMed  Google Scholar 

  9. Haga HJ, Brun JG, Berntzen HB, Cervera R, Khamashta M, Hughes GR. Calprotectin in patients with systemic lupus erythematosus: relation to clinical and laboratory parameters of disease activity. Lupus 1993;2:47–50.

    Article  CAS  PubMed  Google Scholar 

  10. Hammer HB, Odegard S, Fagerhol MK, Landewé R, van der Heijde D, Uhlig T, et al. Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis. Ann Rheum Dis 2007;66:1093–1097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hammer HB, Odegard S, Syversen SW, Landewé R, van der Heijde D, Uhlig T, et al. Calprotectin (a major S100 leukocyte protein) predicts 10-year radiographic progression in patients with rheumatoid arthritis. Ann Rheum Dis 2010;69:150–154.

    Article  CAS  PubMed  Google Scholar 

  12. Andres Cerezo L, Mann H, Pecha O, Plestilova L, Pavelka K, Vencovsky J, 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:R122.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Andrés Cerezo L, Mann H, Pecha O, Pleštilová L, Pavelka K, Vencovský J, Šenolt L. 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:R122.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wakefield RJ, Goh E, Conaghan PG, Karim Z, Emery P. Musculoskeletal ultrasonography in Europe: results of a rheumatologist-based survey at a EULAR meeting. Rheumatology (Oxford) 2003;42:1251–1253.

    Article  CAS  Google Scholar 

  15. Saleem B, Brown AK, Quinn M, Karim Z, Hensor EM, Conaghan P et al. Can flare be predicted in DMARD treated RA patients in remission, and is it important?. A cohort study. Ann Rheum Dis 2012;71:1316–1321.

    Article  PubMed  Google Scholar 

  16. Hammer HB, Fagerhol MK, Wien TN, Kvien TK. The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographicsynovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab. Arthritis Res Ther 2011;13:R178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO3rd, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010;62:2569–2581.

    Article  PubMed  Google Scholar 

  18. Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–48.

    Article  CAS  PubMed  Google Scholar 

  19. Van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 1998;41:1845–1850.

    Article  PubMed  Google Scholar 

  20. England JM, Rowan RM, van Assendelft OW, Coulter WH, Groner W, Jones AR et al. Protocol for evaluation of automated blood cell counters. International Committee for Standardization in Haematology (ICSH). Clin Lab Haematol 1984;6:69–84.

    CAS  PubMed  Google Scholar 

  21. Westergren A. Studies of suspension stability of the blood in pulmonary tuberculosis. Am Rev Tuberc 1921;14:94–97.

    Google Scholar 

  22. Backhaus M, Burmester GR, Gerber T, Grassi W, Machold KP, Swen WA, et al. Guidelines for musculoskeletal ultrasound in rheumatology. Ann Rheum Dis 2001;60:641–649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Naredo E, Rodríguez M, Campos C, Rodríguez-Heredia JM, Medina JA, Giner E et al. Validity, reproducibility, and responsiveness of a twelve-joint simplified power Doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis. Arthritis Rheum 2008;59:515–522.

    Article  PubMed  Google Scholar 

  24. Youssef P, Roth J, Frosch M, Costello P, Fitzgerald O, Sorg C, Bresnihan B. Expression of myeloid related proteins (MRP) 8 and 14 and the MRP8/14 heterodimer in rheumatoid arthritis synovial membrane. J Rheumatol 1999;26:2523–2528.

    CAS  PubMed  Google Scholar 

  25. Brun JG, Haga HJ, Boe E, Kallay I, Lekven C, Berntzen HB, et al. Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity. J Rheumatol 1992;19:859–862.

    CAS  PubMed  Google Scholar 

  26. Garcia-Arias M, Pascual-Salcedo D, Ramiro S, Ueberschlag ME, Jermann TM, Cara C et al. Calprotectin in rheumatoid arthritis: association with disease activity in a cross-sectional and a longitudinal cohort. Mol Diagn Ther 2013;17:49–56.

    Article  CAS  PubMed  Google Scholar 

  27. Foell D, Wulffraat N, Wedderburn LR, Wittkowski H, Frosch M, Gerss J, et al. Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA 2010;303:1266–1273.

    Article  CAS  PubMed  Google Scholar 

  28. Hurnakova J, Zavada J, Hanova P, Hulejova H, Klein M, Mann H et al. Serumcalprotectin (S100A8/9): an independentpredictor of ultrasoundsynovitis in patients with rheumatoidarthritis. Arthritis Res Ther 2015;17:252.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Colebatch AN, Edwards CJ, Ostergaard M, van der Heijde D, Balint PV, D’Agostino MA, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis 2013;72:804–814.

    Article  PubMed  Google Scholar 

  30. Kane D, Roth J, Frosch M, Vogl T, Bresnihan B, FitzGerald O. Increased perivascular synovial membrane expression of myeloid-related proteins in psoriatic arthritis. Arthritis Rheum 2003;48:1676–1685.

    Article  CAS  PubMed  Google Scholar 

  31. Frosch M, Strey A, Vogl T, Wulffraat NM, Kuis W, Sunderkötter C, 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 pauciarticularonset juvenile rheumatoid arthritis. Arthritis Rheum 2000;43:628–637.

    Article  CAS  PubMed  Google Scholar 

  32. Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E et al. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression. Arthritis Rheum 2006;54:3761–3773.

    Article  CAS  PubMed  Google Scholar 

  33. Naredo E, Möller I, Cruz A, Carmona L, Carrido J. Power Doppler ultrasonographic monitoring of response to anti-tumor necrosis factor therapy in patients with rheumatoid arthritis. Arthritis Rheum 2008;58:2248–2256.

    Article  PubMed  Google Scholar 

  34. Hammer HB, Haavardsholm EA, Kvien TK. Calprotectin (a major leucocyte protein) is associated with the levels of anti-CCP and rheumatoid factor in a longitudinal study of patients with very early rheumatoid arthritis. Scand J Rheumatol 2008;37:179–182.

    Article  CAS  PubMed  Google Scholar 

  35. Chen YS, 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:R39.

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Physical Medicine and Rheumatology, Benha Faculty of Medicine, Benha University, Al Yasmin 8, Villa 1, Banha, 1347, Egypt

    Amal F. Soliman & Basant M. Elnady MD

  2. Clinical and Chemical Pathology, Benha Faculty of Medicine, Benha University, Banha, Egypt

    Amira I. Mansour

  3. Department of Public Health, Benha Faculty of Medicine, Benha University, Banha, Egypt

    Raneyah H. Mahmoud Shaker

Authors
  1. Amal F. Soliman
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  2. Basant M. Elnady MD
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  3. Raneyah H. Mahmoud Shaker
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  4. Amira I. Mansour
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Correspondence to Basant M. Elnady MD.

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Soliman, A.F., Elnady, B.M., Shaker, R.H.M. et al. Potential role of calprotectin as a monitoring biomarker for clinical and sonographic activity and treatment outcome in recent-onset rheumatoid arthritis. Egypt Rheumatol Rehabil 43, 143–149 (2016). https://doi.org/10.4103/1110-161X.189824

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  • DOI: https://doi.org/10.4103/1110-161X.189824

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