Abstract
Rheumatoid arthritis (RA) is a chronic, inflammatory, and autoimmune disease that can cause permanent joint damage. In our study, we aim to analyze the change in calprotectin levels following the low-density exercise levels applied to the patients with RA. Twenty-eight patients with RA and 30 healthy controls were included in this study. To evaluate the activity of disease in RA, scores of disease activity that has increased (DAS-28) are figured. Calprotectin, nitric oxide (NO), white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF) levels are tested as the laboratory evaluation. Calprotectin, NO, CRP, ESR, WBC, and RF levels were significantly higher in the patient group compared to the control group (p < 0.01, p < 0.001, p < 0.01, p < 0.01, p < 0.01, and p < 0.05, respectively). In correlation analysis applied to the patient group with RA, there has been determined a positive relation with calprotectin, and DAS-28, CRP, NO, RF, and WBC (p < 0.001, p < 0.05, p < 0.001, p < 0.05, and p < 0.05, respectively). In result of the low-density exercise treatment applied to patients with RA for 8 weeks, there has been determined a significant decrease in calprotectin, DAS-28, NO, CRP, ESR, and RF levels (p < 0.05, p < 0.001, p < 0.01, p < 0.05, p < 0.05, and p < 0.05, respectively). As a result, a significant relation is found between RA disease activity and calprotectin levels and other inflammatory parameters. At the same time, it shows that calprotectin which is a significant indicator of local inflammation can be used as a good identifier in following up exercise treatment.
Similar content being viewed by others
References
Alamanos Y, Drosos AA (2005) Epidemiology of adult rheumatoid arthritis. Autoimmum Rev 4:130–136. doi:10.1016/j.autrev.2004.09.002
Minnock P, Fitzgerald O, Bresnihan B (2003) Women with established rheumatoid arthritis perceive pain as the predominant impairment of health status. Rheumatology 42:995–1000. doi:10.1093/rheumatology/keg281
Sattar N, Mccarey DW, Capell H, Mcinnes IB (2003) Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation 108:2957–2963. doi:10.1161/01.CIR.0000099844.31524.05
Van Leeuwen MA, Westra J, Limburg PC, Van Riel PLCM, Rijswijk MH (1995) 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 Therheumatic Dis 54:674–677. doi:10.1136/ard.54.8.674
Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, Latinis K, Abud-Mendoza C, Szczepański LJ, Roschmann RA, Chen A, Armstrong GK, Douglass W, Tyrrell H (2010) Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naïve with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis 69:1629–1635. doi:10.1136/ard.2009.119933
Cesaro A, Anceriz N, Plante A, Page N, Tardif MR, Tessier PA (2012) An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. Plos One 7:45478. doi:10.1371/journal.pone.0045478
Youssef P, Roth J, Frosch M, Costello P, Fitzgerald O, Sorg C, Bresnihan B (1999) Expression of myeloid related proteins (mrp) 8 and 14 and the mrp8/14 heterodimer in rheumatoid arthritis synovial membrane. J Rheumatol 26:2523–2528
Weinblatt ME, Kremer JM, Coblyn JS, Maier AL, Helfgot SM, Morrell M, Byrne VM, Kaymakcian MV, Strand V (1999) Pharmacokinetics, safety, and efficacy of combination treatment with metotrexate and leflunamide in patients with active rheumatoid arthritis. Arthritis Rheum 42:1322–1328. doi:10.1002/1529-0131(199907)42:7<1322::AID-ANR4>3.0.CO;2-P
Malemud CJ (2011) Myeloid-related protein activity in rheumatoid arthritis. Sage-Hindawi Access to Research İnternational journal of Inflammation Article ID 580295. Doi:10.4061/2011/580295
Nakamura H, Ueki Y, Sakito S, Matsumoto K, Yano M, Miyake S, Tominaga Y, Eguchi K (2000) Clinical effects of actarit in rheumatoid arthritis: improvement of early disease activity mediated by reduction of serum concentrations of nitric oxide. Clin Exp Rheumatol 18(4):445–450
Stewart LK, Flynn MG, Campbell WW, Craig BA, Robinson JP, Timmerman KL, Mcfarlin BK, Coen PM, Talbert E (2007) The influence exercise training on inflammatory cytokines and C-reactive protein. Med Sci Sports Exerc 39(10):1714–1719. doi:10.1249/mss.0b013e31811ece1c
Gualano B, Pinto AL, Perondi BM, Roschel H, Sallum AM, Hayashi AP, Solis MY, Silva CA (2011) Therapeutic effects of exercise training in patients with pediatric rheumatic diseases. Rev Bras Reumatol 51:490–496. doi:10.1590/S0482-50042011000500008
Aletaha D, Neogi T, Silman A et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581. doi:10.1002/art.27580
Kiely P, Walsh D, Williams R, Young A, Early Rheumatoid Arthritis Network (2011) Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate disease activity—the early RA network (ERAN). Rheumatology (Oxford) 50(5):926–931. doi:10.1093/rheumatology/keq406
Hammer HB, Fagerhol MK, Wien TN, Kvien TK (2011) The soluble biomarker calprotectin (an s100 protein) is associated to ultrasonographic synovitis scoresand is sensitive to change in patients with rheumatoid arthritis treated with a dalimumab. Arthritis Res Ther 13(5):r178. doi:10.1186/ar3503
Newton RA, Hogg N (1998) The human S100 protein MRP-14 is a novel activator of the beta 2 integrin Mac-1 on neutrophils. J Immunol 160:1427–1435
Frosch M, Strey A, Vogl T, Wulffraat NM, Kuis W, Sunderkötter C, Harms E, Sorg C, Roth J (2000) 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 43(3):628–637. doi:10.1002/1529-0131(200003)43:3<628::AID-ANR20>3.0.CO;2-X
Ryckman C, McColl SR, Vandal K, de Médicis R, Lussier A, Poubelle PE, Tessier PA (2003) Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis. Arthritis Rheum 48:2310–2320. doi:10.1002/art.11079
Foell D, Roth J (2004) Proinflammatory s100 proteins in arthritis and auto-immune disease. Arthritis Rheum 50:3762–3771. doi:10.1002/art.20631
Hammer HB, Odegard S, Fagerhol MK, Landewé R, van der Heijde D, Uhlig T, Mowinckel P, Kvien TK (2007) Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis. Ann Rheum Dis 66(8):1093–1097. doi:10.1136/ard.2006.064741
Adel N, William M, Swaff RA, Hassan S (2014) Serum calprotectin level for diagnosis and detection of disease activity in rheumatoid arthritis. Int J Immunol 2(1):6–10. doi:10.11648/j.iji.20140201.12
Berntzen HB, Olmez U, Fagerhol MK, Munthe E (1991) The leukocyte protein L1 in plasma and synovial fluid from patients with rheumatoid arthritis and osteoarthritis. Scand J Rheumatol 20(2):74–82. doi:10.3109/03009749109165280
Brun JG, Jonsson R, Haga HJ (1994) Measurement of plasma calprotectin as an indicator of arthritis and disease activity in patients with inflammatory rheumatic diseases. J Rheumatol 21(4):733–738
García-Arias M, Pascual-Salcedo D, Ramiro S, Ueberschlag ME, Jermann TM, Cara C, Martín-Mola E, Balsa A (2013) Calprotectin in rheumatoid arthritis: association with disease activity in a cross-sectional and a longitudinal cohort. Mol Diagn Ther 17(1):49–56. doi:10.1007/s40291-013-0016-9
Choi IY, Gerlag DM, Herenius MJ, Thurlings RM, Wijbrandts CA, Foell D, Vogl T, Roth J, Tak PP, Holzinger D (2015) MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis. Ann Rheum Dis 74(3):499–505. doi:10.1136/annrheumdis-2013-203923
Baillet A, Trocmé C, Berthier S, Arlotto M, Grange L, Chenau J, Quétant S, Sève M, Berger F, Juvin R, Morel F, Gaudin P (2010) Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases. Rheumatology (Oxford) 49(4):671–682. doi:10.1093/rheumatology/kep452
Farrell AJ, Blake DR, Palmer RM, Moncada S (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 51(11):1219–1222
Ueki Y, Miyake S, Tominaga Y, Eguchi K (1996) Increased nitric oxide levels in patients with rheumatoid arthritis. J Rheumatol 23(2):230–236
Holzinger D, Frosch M, Kastrup A, Prince FH, Otten MH, Van Suijlekom-Smit LW, ten Cate R, Hoppenreijs EP, Hansmann S, Moncrieffe H, Ursu S, Wedderburn LR, Roth J, Foell D, Wittkowski H (2012) The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis. Ann Rheum Dis 71(6):974–980. doi:10.1136/annrheumdis-2011-200598
Stefanovic-Racic M, Stadler J, Evans CH (1993) Nitric oxide and arthritis. Arthritis Rheum 36(8):1036–1044. doi:10.1002/art.1780360803
Wells G, Li T, Maxwell L, Maclean R, Tugwell P (2008) Responsiveness of patient reported outcomes including fatigue, sleep quality, activity limitation, and quality of life following treatment with abatacept for rheumatoid arthritis. Ann Rheum Dis 67:260–265
Böttiger LE, Svedberg CA (1967) Normal erythrocyte sedimentation rate and age. Br Med J 2:85–87
Kushner I (1991) C-reactive protein in rheumatology. Arthritis Rheum 34:1065–1068
Pincus T, Braun J, Kavanaugh A, Smolen JS (2014) Optimisation of assessment for rheumatic diseases in clinical trials, observational studies and routine clinical care. Clin Exp Rheumatol 32: S–1
Andrés Cerezo L, Mann H, Pecha O, Pleštilová L, Pavelka K, Vencovský J, Senolt L (2011) 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 13(4):R122. doi:10.1186/ar3426
Metsios GS, Stavropoulos-Kalinoglou (2008) Rheumatoid arthritis, cardiovascular disease and physical exercise: a systematic review. Rheumatology (Oxford) 47(3):239–248. doi:10.1093/rheumatology/kem260
Lyngberg KK, Harreby M, Bentzen H, Frost B, Danneskiold-Samsøe B (1994) Elderly rheumatoid arthritis patients on steroid treatment tolerate physical training without an increase in disease activity. Arch Phys Med Rehabil 75(11):1189–1195
Wadley AJ, Veldhuijzen van Zanten JJ, Stavropoulos-Kalinoglou A, Metsios GS, Smith JP, Kitas GD, Aldred S (2014) Three months of moderate-intensity exercise reduced plasma 3-nitrotyrosine in rheumatoid arthritis patients. Eur J Appl Physiol 114(7):1483–1492. doi:10.1007/s00421-014-2877-y
Okita K, Nishijima H, Murakami T, Nagai T, Morita N, Yonezawa K, Iizuka K, Kawaguchi H, Kitabatake A (2004) Can exercise training with weight loss lower serum C-reactive protein levels? Arterioscler Thromb Vasc Biol 24(10):1868–1873. doi:10.1161/01.ATV.0000140199.14930.32
Kelley GA, Kelley KS (2006) Effects of aerobic exercise on C-reactive protein, body composition, and maximum oxygen consumption in adults: a meta-analysis of randomized controlled trials. Metabolism 55(11):1500–1507. doi:10.1016/j.metabol.2006.06.021
Nader GA, Lundberg IE (2009) Exercise as an anti-inflammatory intervention to combat inflammatory diseases of muscle. Curr Opin Rheumatol 21(6):599–603. doi:10.1097/BOR.0b013e3283319d53
Vogiatzis I, Stratakos G, Simoes DC, Terzis G, Georgiadou O, Roussos C, Zakynthinos S (2007) Effects of rehabilitative exercise on peripheral muscle TNFalpha, IL-6, IGF-I and MyoD expression in patients with COPD. Thorax 62(11):950–956. doi:10.1136/thx.2006.069310
Trøseid M, Lappegård KT, Claudi T, Damås JK, Mørkrid L, Brendberg R, Mollnes TE (2004) Exercise reduces plasma levels of the chemokines MCP-1 and IL-8 in subjects with the metabolic syndrome. Eur Heart J 25(4):349–355. doi:10.1016/j.ehj.2003.12.006
Adamopoulos S, Parissis J, Kroupis C, Georgiadis M, Karatzas D, Karavolias G, Koniavitou K, Coats AJ, Kremastinos DT (2001) Physical training reduces peripheral markers of inflammation in patients with chronic heart failure. Eur Heart J 22(9):791–797. doi:10.1053/euhj.2000.2285
Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovich CF (2001) Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J 15(2):475–482. doi:10.1096/fj.00-0274com
Neuberger GB, Press AN, Lindsley HB, Hinton R, Cagle PE, Carlson K, Scott S, Dahl J, Kramer B (1997) Effects of exercise on fatigue, aerobic fitness, and disease activity measures in persons with rheumatoid arthritis. Res Nurs Health 20(3):195–204. doi:10.1002/(SICI)1098-240X(199706)20:3<195::AID-NUR3>3.0.CO;2-D
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was approved by the local ethics Committee on Human Research, and all patients gave written informed consent.
Disclosures
None.
Rights and permissions
About this article
Cite this article
Acar, A., Guzel, S., Sarifakioglu, B. et al. Calprotectin levels in patients with rheumatoid arthritis to assess and association with exercise treatment. Clin Rheumatol 35, 2685–2692 (2016). https://doi.org/10.1007/s10067-016-3240-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-016-3240-y