Background. Although the benchmark in the treatment of rheumatoid arthritis remains methotrexate, only 70% of patients respond. Thus, there is a need for predictive biomarkers. This study planned to evaluate serum levels of myeloid progenitor inhibitory factor-1 (MPIF-1) and monocyte chemoattractant protein 2 (MCP-2)—as biomarkers. Methods. Patients with rheumatoid arthritis (RA) having high disease activity (DAS28-3v？≥？5.1) were treated with oral methotrexate (MTX) for 12 weeks. Disease activity was measured by DAS28-3v (Modified Disease Activity Score 3 variables). Serum samples were stored at baseline and 12 weeks. Results. This study included 46 patients (F？:？M = 35？:？11) having mean (±SD) age of 42.6 ± 11.3？yrs, disease duration of 4.7 ± 4.5？yrs, and DAS28-3v of 6.1 ± 0.8. Serum MPIF1 was elevated in patients compared to controls (1636.7 ± 1009.7, 441.2 ± 173.8？pg/mL, ), but there was no difference in MCP2 levels (31.4 ± 11.9, 33.8 ± 24.0？pg/mL). Baseline MPIF-1 level was lower in good responders (ΔDAS28-3v？≥？1.2, ) compared to poor responders (ΔDAS28-3v？<？0.6, ) (1171.0 ± 670.8, 1816.7 ± 1154.1？pg/mL, ). On ROC analysis, baseline MPIF1 performed reasonably to predict good response; that is, ΔDAS28-3v？≥？1.2 (AUC 0.68, 95% CI 0.50–0.87). Conclusions. Lower baseline MPIF1 level predicted a good response to methotrexate at 12 weeks. 1. Introduction Rheumatoid arthritis is an autoimmune chronic inflammatory disease predominantly affecting the joints [1]. There is a recent emphasis on a “treat to target” strategy, with regular monitoring of disease activity and quick adjustments of drugs [2]. Although joint assessment remains the gold standard for disease activity, biomarkers may come to play a complementary role [3]. In the treatment of RA, the benchmark drug remains methotrexate. However, it is effective in only 70% of patients, and an excellent response is seen in only 30% of patients. A common therapeutic strategy is to start with methotrexate, and patients who do not respond to methotrexate are subsequently shifted to other drugs or combinations (other DMARDs or biologicals). However, waiting for response to methotrexate may delay institution of other effective therapies in nonresponders and contribute to joint damage. Thus, there is a need to identify nonresponders to methotrexate upfront to institute other therapies [4] hence the need for activity and predictive biomarkers [5]. Chemokines are small proteins involved in chemoattraction of a variety of cells to site of inflammation, being important in the pathogenesis of RA and may serve as
References
[1]
D. L. Scott, F. Wolfe, and T. W. J. Huizinga, “Rheumatoid arthritis,” The Lancet, vol. 376, no. 9746, pp. 1094–1108, 2010.
[2]
J. S. Smolen, D. Aletaha, J. W. Bijlsma et al., “Treating rheumatoid arthritis to target: recommendations of an international task force,” Annals of the Rheumatic Diseases, vol. 69, no. 4, pp. 631–637, 2010.
[3]
T. Sokka and T. Pincus, “Quantitative joint assessment in rheumatoid arthritis,” Clinical and Experimental Rheumatology, vol. 23, no. 5, pp. S58–S62, 2005.
[4]
T. Pincus, Y. Yazici, T. Sokka, D. Aletaha, and J. S. Smolen, “Methotrexate as the “anchor drug” for the treatment of early rheumatoid arthritis,” Clinical and Experimental Rheumatology, vol. 21, no. 5, pp. S179–S185, 2003.
[5]
P. J. Mease, “The potential roles for novel biomarkers in rheumatoid arthritis assessment,” Clinical and Experimental Rheumatology, vol. 29, no. 3, pp. 567–574, 2011.
[6]
A. D. Luster, “Chemokines—chemotactic cytokines that mediate inflammation,” The New England Journal of Medicine, vol. 338, no. 7, pp. 436–445, 1998.
[7]
P. Proost, A. Wuyts, and J. van Damme, “Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1,” Journal of Leukocyte Biology, vol. 59, no. 1, pp. 67–74, 1996.
[8]
W. Gong, O. M. Z. Howard, J. A. Turpin et al., “Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication,” The Journal of Biological Chemistry, vol. 273, no. 8, pp. 4289–4292, 1998.
[9]
V. P. Patel, B. L. Kreider, Y. Li et al., “Molecular and functional characterization of two novel human C-C chemokines as inhibitors of two distinct classes of myeloid progenitors,” Journal of Experimental Medicine, vol. 185, no. 7, pp. 1163–1172, 1997.
[10]
R. D. Berahovich, Z. Miao, Y. Wang, B. Premack, M. C. Howard, and T. J. Schall, “Proteolytic activation of alternative CCR1 ligands in inflammation,” Journal of Immunology, vol. 174, no. 11, pp. 7341–7351, 2005.
[11]
I. Rioja, F. J. Hughes, C. H. Sharp et al., “Potential novel biomarkers of disease activity in rheumatoid arthritis patients: CXCL13, CCL23, transforming growth factor α, tumor necrosis factor receptor superfamily member 9, and macrophage colony-stimulating factor,” Arthritis and Rheumatism, vol. 58, no. 8, pp. 2257–2267, 2008.
[12]
F. C. Arnett, S. M. Edworthy, D. A. Bloch et al., “The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis,” Arthritis and Rheumatism, vol. 31, no. 3, pp. 315–324, 1988.
A. Kumar, A. N. Malaviya, A. Pandhi, and R. Singh, “Validation of an Indian version of the health assessment questionnaire in patients with rheumatoid arthritis,” Rheumatology, vol. 41, no. 12, pp. 1457–1459, 2002.
[15]
J. J. Haringman, T. J. M. Smeets, P. Reinders-Blankert, and P. P. Tak, “Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis,” Annals of the Rheumatic Diseases, vol. 65, no. 3, pp. 294–300, 2006.
[16]
M. Bulatovi？, M. W. Heijstek, E. H. P. van Dijkhuizen, N. M. Wulffraat, S. M. F. Pluijm, and R. de Jonge, “Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis,” Annals of the Rheumatic Diseases, vol. 71, no. 9, pp. 1484–1489, 2012.
[17]
J. Drouin, B. Haraoui, and 3e Initiative Group, “Predictors of clinical response and radiographic progression in patients with rheumatoid arthritis treated with methotrexate monotherapy,” Journal of Rheumatology, vol. 37, no. 7, pp. 1405–1410, 2010.
[18]
W. Katchamart, S. Johnson, H. L. Lin, V. Phumethum, C. Salliot, and C. Bombardier, “Predictors for remission in rheumatoid arthritis patients: a systematic review,” Arthritis Care and Research, vol. 62, no. 8, pp. 1128–1143, 2010.
[19]
S. L. Hider, A. J. Silman, W. Thomson, M. Lunt, D. Bunn, and D. P. M. Symmons, “Can clinical factors at presentation be used to predict outcome of treatment with methotrexate in patients with early inflammatory polyarthritis?” Annals of the Rheumatic Diseases, vol. 68, no. 1, pp. 57–62, 2009.
[20]
M. Pierer, J. Rethage, R. Seibl et al., “Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by toll-like receptor 2 ligands,” Journal of Immunology, vol. 172, no. 2, pp. 1256–1265, 2004.
[21]
J. S. Smolen, R. Landewé, F. C. Breedveld et al., “EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs,” Annals of the Rheumatic Diseases, vol. 69, no. 6, pp. 964–975, 2010.
[22]
J. A. Singh, D. E. Furst, A. Bharat et al., “2012 update of the 2008 American college of rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis,” Arthritis Care and Research, vol. 64, no. 5, pp. 635–639, 2012.
[23]
R. van Vollenhoven, S. Ernestam, P. Geborek et al., “Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial,” The Lancet, vol. 374, no. 9688, pp. 459–466, 2009.
