Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

Cells - Tập 7 Số 10 - Trang 161
Hooi-Yeen Yap1,2, Sabrina Tee1, Magdelyn Wong1, S K Chow1,2,3, Suat‐Cheng Peh1,2,3, Sin‐Yeang Teow1,2
1Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University,
2Jalan Universiti, Bandar Sunway, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia;
3Sunway Medical Centre, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia

Tóm tắt

Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient’s response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers.

Từ khóa


Tài liệu tham khảo

(2018, February 15). Chronic Rheumatic Conditions. Available online: http://www.who.int/chp/topics/rheumatic/en/.

Ferri, F.F. (2018). Rheumatoid arthritis. Ferri’s Clinical Advisor, Elsevier. [20th ed.].

Kellerman, R.D., and Bope, E.T. (2018). Rheumatoid arthritis. Conn’s Current Therapy, Elsevier. [70th ed.].

Brassard, 2006, Antirheumatic drugs and the risk of tuberculosis, Clin. Inf. Dis., 43, 717, 10.1086/506935

Navarra, 2014, Risk of tuberculosis with anti-tumor necrosis factor-α therapy: Substantially higher number of patients at risk in Asia, Int. J. Rheum. Dis., 17, 291, 10.1111/1756-185X.12188

Mewar, 2011, Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors, Br. J. Pharmacol., 162, 785, 10.1111/j.1476-5381.2010.01099.x

Dixon, 2010, Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: Results from the British Society for Rheumatology Biologics Register (BSRBR), Ann. Rheum. Dis., 69, 522, 10.1136/ard.2009.118935

(2018, February 27). Rheumatoid Arthritis Treatment. Available online: http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/.

Semerano, 2016, Developments with investigational Janus kinase inhibitors for rheumatoid arthritis, Expert Opin. Investig. Drugs, 25, 1355, 10.1080/13543784.2016.1249565

Monti, 2015, Rheumatoid arthritis treatment: The earlier the better to prevent joint damage, RMD Open, 1, e000057, 10.1136/rmdopen-2015-000057

Bugatti, 2014, B cells in rheumatoid arthritis: From pathogenic players to disease biomarkers, BioMed Res. Int., 2014, 681678, 10.1155/2014/681678

Giltiay, 2012, B-cell selection and the development of autoantibodies, Arthritis Res. Ther., 14, S1, 10.1186/ar3918

Browne, 2012, Regulation of B-cell responses by Toll-like receptors, Immunology, 136, 370, 10.1111/j.1365-2567.2012.03587.x

Samuels, 2005, Impaired early B cell tolerance in patients with rheumatoid arthritis, J. Exp. Med., 201, 1659, 10.1084/jem.20042321

Meffre, 2011, The establishment of early B cell tolerance in humans: Lessons from primary immunodeficiency diseases, Ann. N. Y. Acad. Sci., 1246, 1, 10.1111/j.1749-6632.2011.06347.x

Menard, 2011, Inflammation-independent defective early B cell tolerance checkpoints in rheumatoid arthritis, Arthritis Rheum., 63, 1237, 10.1002/art.30164

Ehrenstein, 2004, Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy, J. Exp. Med., 200, 277, 10.1084/jem.20040165

Rapetti, 2015, B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis, Ann. Rheum. Dis., 74, 294, 10.1136/annrheumdis-2013-204049

Mackay, 2009, Cracking the BAFF code, Nat. Rev. Immunol., 9, 491, 10.1038/nri2572

Aarvak, 2011, Cell-cell interactions in synovitis: Antigen presenting cells and T cell interaction in rheumatoid arthritis, Arthritis Res., 3, 13, 10.1186/ar135

Schlegel, P.M., Steiert, I., Kötter, I., and Müller, C.A. (2013). B cell contribute to heterogeneity of IL-17 producing cells in rheumatoid arthritis and healthy controls. PLoS ONE, 8.

Nakagawa, 1998, RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis, Biochem. Biophys. Res. Commun., 253, 395, 10.1006/bbrc.1998.9788

Cope, 2007, The central role of T cells in rheumatoid arthritis, Clin. Exp. Rheumatol., 25, S4

Meednu, 2016, Production of RANKL by memory B cells: A link between B cells and bone erosion in rheumatoid arthritis, Arthritis Rheumatol., 68, 805, 10.1002/art.39489

Podojil, 2009, Molecular mechanisms of T cell receptor and costimulatory molecule ligation/blockade in autoimmune disease therapy, Immunol. Rev., 229, 337, 10.1111/j.1600-065X.2009.00773.x

Williams, 2007, Effector and memory CTL differentiation, Annu. Rev. Immunol., 25, 171, 10.1146/annurev.immunol.25.022106.141548

Cope, 2008, T cells in rheumatoid arthritis, Arthritis Res. Ther., 10, S1, 10.1186/ar2412

Kalden, 2001, The balance of Th1/Th2 cytokines in rheumatoid arthritis, Best Pract. Res. Clin. Rheumatol., 15, 677, 10.1053/berh.2001.0187

Alunno, 2015, Altered immunoregulation in rheumatoid arthritis: The role of regulatory T cells and proinflammatory Th17 cells and therapeutic implications, Mediat. Inflamm., 2015, 751793, 10.1155/2015/751793

Hussein, 2016, Th-17 cells and serum IL-17 in rheumatoid arthritis patients: Correlation with disease activity and severity, Egypt. Rheumatol., 38, 1, 10.1016/j.ejr.2015.01.001

Suurmond, 2011, Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium, Arthritis Res. Ther., 13, R150, 10.1186/ar3466

Gaffen, 2009, Role of IL-17 in the pathogenesis of rheumatoid arthritis, Curr. Rheumatol. Rep., 11, 365, 10.1007/s11926-009-0052-y

Ciccia, 2015, Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis, Rheumatology (Oxford), 54, 2264, 10.1093/rheumatology/kev252

Chowdhury, 2018, Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis, Arthritis Res. Ther., 20, 18, 10.1186/s13075-017-1505-8

Cooles, 2013, Treg cells in rheumatoid arthritis: An update, Curr. Rheumatol. Rep., 15, 352, 10.1007/s11926-013-0352-0

Boissier, 2009, Regulatory T cells (Treg) in rheumatoid arthritis, Jt. Bone Spine, 79, 10, 10.1016/j.jbspin.2008.08.002

Morita, T., Shima, Y., Wing, J.B., Sakaguchi, S., Ogata, A., and Kumanogoh, A. (2016). The proportion of regulatory T cells in patients with rheumatoid arthritis: A meta-analysis. PLoS ONE, 11.

Mamdouh, 2015, FoxP3+T regulatory cells in rheumatoid arthritis and the imbalance of the Treg/TH17 cytokine axis, Egypt. Rheumatol., 37, 7, 10.1016/j.ejr.2014.06.004

Rao, 2018, T cells that help B cells in chronically inflamed tissues, Front. Immunol., 9, 1924, 10.3389/fimmu.2018.01924

Rao, 2017, Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis, Nature, 542, 110, 10.1038/nature20810

Kinne, 2000, Macrophages in rheumatoid arthritis, Arthritis Res., 2, 189, 10.1186/ar86

Bondeson, 2006, The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis, Arthritis Res. Ther., 8, R187, 10.1186/ar2099

Davignon, 2013, Targeting monocytes/macrophages in the treatment of rheumatoid arthritis, Rheumatology (Oxford), 52, 590, 10.1093/rheumatology/kes304

Kim, 2010, Targeted delivery of siRNA to macrophages for anti-inflammatory treatment, Mol. Ther., 18, 993, 10.1038/mt.2010.27

Onuora, 2018, Experimental arthritis: Anti-TNF kills the macrophage response, Nat. Rev. Rheumatol., 14, 64

Pham, 2011, Nanotherapeutic approaches for the treatment of rheumatoid arthritis, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 3, 607, 10.1002/wnan.157

Rivellese, 2017, Mast cells in rheumatoid arthritis: Friends or foes?, Autoimmun. Rev., 16, 557, 10.1016/j.autrev.2017.04.001

Yu, 2017, The function of myeloid dendritic cells in rheumatoid arthritis, Rheumatol. Int., 37, 1043, 10.1007/s00296-017-3671-z

Khan, 2009, Dendritic cells as targets for therapy in rheumatoid arthritis, Nat. Rev. Rheumatol., 5, 566, 10.1038/nrrheum.2009.185

Hilkens, 2013, Tolerogenic dendritic cell therapy for rheumatoid arthritis: Where are we now?, Clin. Exp. Immunol., 172, 148, 10.1111/cei.12038

Shegarfi, 2012, Natural killer cells and their role in rheumatoid arthritis: Friend or foe?, Sci. World J., 2012, 491974, 10.1100/2012/491974

Feldmann, 1996, Role of cytokines in rheumatoid arthritis, Annu. Rev. Immunol., 14, 397, 10.1146/annurev.immunol.14.1.397

Brzustewicz, 2015, The role of cytokines in the pathogenesis of rheumatoid arthritis—Practical and potential application of cytokines as biomarkers and targets of personalized therapy, Cytokine, 76, 527, 10.1016/j.cyto.2015.08.260

Burska, 2014, Cytokines as Biomarkers in Rheumatoid Arthritis, Med. Inflamm., 2014, 545493, 10.1155/2014/545493

Alam, 2017, Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy, Biomed. Pharmacother., 92, 615, 10.1016/j.biopha.2017.05.055

Mateen, 2016, Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis, Clin. Chim. Acta, 455, 161, 10.1016/j.cca.2016.02.010

Choy, 2012, Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis, Rheumatology (Oxford), 51, v3, 10.1093/rheumatology/kes113

Griesmacher, 2001, Autoantibodies associated with rheumatic diseases, Clin. Chem. Lab. Med., 39, 189, 10.1515/CCLM.2001.031

Song, 2010, Autoantibodies in rheumatoid arthritis: Rheumatoid factors and anticitrullinated protein antibodies, QJM-Int. J. Med., 103, 139, 10.1093/qjmed/hcp165

Tseng, 2018, High levels of soluble GPR56/ADGRG1 are associated with positive rheumatoid factor and elevated tumor necrosis factor in patients with rheumatoid arthritis, J. Microbiol. Immunol. Infect., 51, 485, 10.1016/j.jmii.2016.11.010

Vossenaar, 2002, Autoantibody systems in rheumatoid arthritis: Specificity, sensitivity and diagnostic value, Arthritis Res., 4, 87, 10.1186/ar464

Vossenaar, 2004, Anti-CCP antibodies, a highly specific marker for (early) rheumatoid arthritis, Clin. Appl. Immunol. Rev., 4, 239, 10.1016/j.cair.2003.11.001

Sidorov, 2017, Fc fragments of immunoglobulin G are an inductor of regulatory rheumatoid factor and a promising therapeutic agent for rheumatic diseases, Int. J. Biol. Macromol., 95, 938, 10.1016/j.ijbiomac.2016.10.081

Aggarwal, 2009, Anti-citrullinated peptide antibody (ACPA) assays and their role in the diagnosis of rheumatoid arthritis, Arthritis Rheum., 61, 1472, 10.1002/art.24827

Manca, 2017, Anti-citrullinated peptide antibodies profiling in established rheumatoid arthritis, Jt. Bone Spine, 85, 441, 10.1016/j.jbspin.2017.07.009

Derksen, 2017, The role of autoantibodies in the pathophysiology of rheumatoid arthritis, Semin. Immunopathol., 39, 437, 10.1007/s00281-017-0627-z

Yee, 2015, Anti-CarP antibodies as promising marker to measure joint damage and disease activity in patients with rheumatoid arthritis, Immunol. Res., 61, 24, 10.1007/s12026-014-8560-x

Kumar, 2017, Assessment of anti-CarP antibodies, disease activity and quality of life in rheumatoid arthritis patients on conventional and biological disease-modifying antirheumatic drugs, Reumatologia, 55, 4, 10.5114/reum.2017.66680

Shi, 2015, The specificity of anti-carbamylated protein antibodies for rheumatoid arthritis in a setting of early arthritis, Arthritis Res. Ther., 17, 339, 10.1186/s13075-015-0860-6

Wang, 2015, Keratin 8 is a novel autoantigen of rheumatoid arthritis, Biochem. Biophys. Res. Commun., 465, 665, 10.1016/j.bbrc.2015.07.161

Vossenaar, 2004, Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin, Arthritis Res. Ther., 6, R142, 10.1186/ar1149

Fadda, 2016, Serum matrix metalloproteinase-3 in rheumatoid arthritis patients: Correlation with disease activity and joint destruction, Egypt. Rheumatol., 38, 153, 10.1016/j.ejr.2016.01.001

Niki, Y., Takeuchi, T., Nakayama, M., Nagasawa, H., Kurasawa, T., Yamada, H., Toyama, Y., and Miyamoto, T. (2012). Clinical significance of cartilage biomarkers for monitoring structural joint damage in rheumatoid arthritis patients treated with anti-TNF therapy. PLoS ONE, 7.

Paleolog, 2009, The vasculature in rheumatoid arthritis: Cause or consequence?, Int. J. Exp. Pathol., 90, 249, 10.1111/j.1365-2613.2009.00640.x

Fardellone, 2014, Bone remodelling markers in rheumatoid arthritis, Mediat. Inflamm., 2014, 484280, 10.1155/2014/484280

Heo, 2014, Hyaluronan nanoparticles bearing γ-secretase inhibitor: In vivo therapeutic effects on rheumatoid arthritis, J. Control. Release, 192, 295, 10.1016/j.jconrel.2014.07.057

Paiva, 2017, Matrix metalloproteinases in bone resorption, remodelling, and repair, Prog. Mol. Biol. Transl. Sci., 148, 203, 10.1016/bs.pmbts.2017.05.001

Darweesh, 2010, Serum and synovial cartilage oligomeric matrix protein (COMP) in patients with rheumatoid arthritis and osteoarthritis, Ind. J. Rheumatol., 5, 112, 10.1016/S0973-3698(10)60556-0

Lorenzo, 2017, Quantification of cartilage oligomeric matrix protein (COMP) and a COMP neoepitope in synovial fluid of patients with different joint disorders by novel automated assays, Osteoarthr. Cartil., 25, 1436, 10.1016/j.joca.2017.04.004

Gorman, 2003, B cell depletion in autoimmune disease, Arthritis Res. Ther., 5, S17, 10.1186/ar1007

Choy, 2003, Interleukin 6 receptor as a target for the treatment of rheumatoid arthritis, Ann. Rheum. Dis., 62, ii68, 10.1136/ard.62.suppl_2.ii68

Shaw, 2003, B cell therapy for rheumatoid arthritis: The rituximab (anti-CD20) experience, Ann. Rheum. Dis., 62, ii55, 10.1136/ard.62.suppl_2.ii55

Taylor, 2003, Anti-cytokines and cytokines in the treatment of rheumatoid arthritis, Curr. Pharm. Des., 9, 1095, 10.2174/1381612033454991

Burrage, 2006, Matrix metalloproteinases: Role in arthritis, Front Biosci., 11, 529, 10.2741/1817

Albrecht, 2010, Side effects and management of side effects of methotrexate in rheumatoid arthritis, Clin. Exp. Rheumatol., 28, S95

Guo, 2018, Rheumatoid arthritis: Pathological mechanisms and modern pharmacologic therapies, Bone Res., 6, 15, 10.1038/s41413-018-0016-9

Ma, 2013, TNF inhibitor therapy for rheumatoid arthritis, Biomed. Rep., 1, 177, 10.3892/br.2012.42

Perdriger, 2009, Infliximab in the treatment of rheumatoid arthritis, Biologics, 3, 183

Weinblatt, 2003, Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMADA trial, Arthritis Rheum., 48, 35, 10.1002/art.10697

Haraoui, 2007, Etanercept in the treatment of rheumatoid arthritis, Ther. Clin. Risk Manag., 3, 99, 10.2147/tcrm.2007.3.1.99

Mease, 2011, Certolizumab pegol in the treatment of rheumatoid arthritis: A comprehensive review of its clinical efficacy and safety, Rheumatology (Oxford), 50, 261, 10.1093/rheumatology/keq285

Singh, 2010, Golimumab for rheumatoid arthritis: A systematic review, J. Rheumatol., 37, 1096, 10.3899/jrheum.091466

Mok, 2014, Rituximab for the treatment of rheumatoid arthritis: An update, Drug Des. Dev. Ther., 8, 87

Kaneko, 2013, Tocilizumab in rheumatoid arthritis: Efficacy, safety and its place in therapy, Ther. Adv. Chronic Dis., 4, 15, 10.1177/2040622312466908

Boyce, 2018, Sarilumab: Review of a second IL-6 receptor antagonist indicated for the treatment of rheumatoid arthritis, Ann. Pharmacother., 52, 780, 10.1177/1060028018761599

Ni, 2013, Oral janus kinase inhibitor for the treatment of rheumatoid arthritis: Tofacitinib, ISRN Rheumatol., 2013, 357904, 10.1155/2013/357904

Gras, 2016, Baricitinib: JAK inhibition for rheumatoid arthritis, Drugs Today, 52, 543, 10.1358/dot.2016.52.10.2525742

Langdon, 2018, Regulatory T-cell dynamics with abatacept treatment in rheumatoid arthritis, Int. Rev. Immunol., 37, 206, 10.1080/08830185.2018.1465943

(2018, August 01). Australian New Zealand Clinical Trials Registry Trial Review. Available online: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373425.

(2018, August 03). NIH US National Library of Medicine Clinical Trials.gov, Available online: https://clinicaltrials.gov/ct2/show/NCT03410056.

Crotti, 2017, Spotlight on mavrilimumab for the treatment of rheumatoid arthritis: Evidence to date, Drug Des. Dev. Ther., 11, 211, 10.2147/DDDT.S104233

Schiff, 2015, Efficacy and safety of tabalumab, an anti-BAFF monoclonal antibody, in patients with moderate-to-severe rheumatoid arthritis and inadequate response to TNF inhibitors: Results of a randomised, double-blind, placebo-controlled, phase 3 study, RMD Open, 1, e000037, 10.1136/rmdopen-2014-000037

Huizinga, 2017, Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis, Arthritis Res. Ther., 19, 53, 10.1186/s13075-017-1267-3

Cook, 2018, Investigational therapies targeting the granulocyte macrophage colony-stimulating factor receptor-α in rheumatoid arthritis: Focus on mavrilimumab, Ther. Adv. Musculoskelet. Dis., 10, 29, 10.1177/1759720X17752036

Kivitz, 2016, FRI0209 MORAb-022, an anti-granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody (MAB): Results of the first study in patients with mild-to-moderate rheumatoid arthritis (RA), Ann. Rheum. Dis., 75, 507, 10.1136/annrheumdis-2016-eular.3186

Molfino, 2016, Phase 2, randomised placebo-controlled trial to evaluate the efficacy and safety of an anti-GM-CSF antibody (KB003) in patients with inadequately controlled asthma, BMJ Open, 6, e007709, 10.1136/bmjopen-2015-007709

Smolen, 2015, Efficacy and safety of tabalumab, an anti-B-cell-activating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy: Results from a phase III multicentre, randomised, double-blind study, Ann. Rheum. Dis., 74, 1567, 10.1136/annrheumdis-2014-207090

Mahtani, 2013, Autoimmune markers for the diagnosis of rheumatoid arthritis in primary care: Primary care diagnostic technology update, Br. J. Gen. Pract., 63, 553, 10.3399/bjgp13X673919

(2018, September 19). Lilly Press Release Archives. Available online: http://lilly.mediaroom.com/index.php?s=9042&item=136985.

Luime, 2010, Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review, Ann. Rheum. Dis., 69, 337, 10.1136/ard.2008.103283

Maksymowych, 2014, Serum 14-3-3η is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis, J. Rheumatol., 41, 2104, 10.3899/jrheum.131446

Anderson, 2012, Rheumatoid arthritis disease activity measures: American college of rheumatology recommendations for use in clinical practice, Arthritis Care Res. (Hoboken), 64, 640, 10.1002/acr.21649

(2018, September 19). Study of KB003 in Biologics-Inadequate Rheumatoid Arthritis, Available online: https://clinicaltrials.gov/ct2/results?term=NCT00995449.

Centola, M., Cavet, G., Shen, Y., Ramanujan, S., Knowlton, N., Swan, K.A., Turner, M., Sutton, C., Smith, D.R., and Haney, D.J. (2013). Development of a multi-biomarker disease activity test for rheumatoid arthritis. PLoS ONE, 8.

Hambardzumyan, 2017, A multi-biomarker disease activity score and the choice of second-line therapy in early rheumatoid arthritis after methotrexate failure, Arthritis Rheumatol., 69, 953, 10.1002/art.40019

Curtis, 2017, Reanalysis of the multi-biomarker disease activity score for assessing disease activity in the AMPLEstudy: Comment on the article by Fleischmann et al, Arthritis Rheumatol., 69, 863, 10.1002/art.39981

2011, Predictors of response to biologic therapies in rheumatoid arthritis, Rheumatol. Clin., 7, 141

Lv, Q., Yin, Y., Li, X., Shan, G., Wu, X., Liang, D., Li, Y., and Zhang, X. (2014). The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: A meta-analysis. PLoS ONE, 9.

Fabris, 2010, Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab, Autoimmun. Highlights, 1, 87, 10.1007/s13317-010-0013-5

Marotta, 2014, SAT0070 levels of 14-3-3Eta predict good EULAR response to anti-TNF treatment in patients with rheumatoid arthritis, Ann. Rheum. Dis., 73, 615, 10.1136/annrheumdis-2014-eular.3426

Morozzi, 2007, Low serum level of COMP, a cartilage turnover marker, predicts rapid and high ACR70 response to adalimumab therapy in rheumatoid arthritis, Clin. Rheumatol., 26, 1335, 10.1007/s10067-006-0520-y

Choi, 2015, MRP8/14 serum levels as a strong predictor of response to biological treatments in patients with rheumatoid arthritis, Ann. Rheum. Dis., 74, 499, 10.1136/annrheumdis-2013-203923

Isgren, 2012, High survivin levels predict poor clinical response to infliximab treatment in patients with rheumatoid arthritis, Semin. Arthritis Rheum., 41, 652, 10.1016/j.semarthrit.2011.08.005

Benham, 2015, Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients, Sci. Transl. Med., 7, 290ra87, 10.1126/scitranslmed.aaa9301

Shabahang, 2010, Recent patents on immunoregulatory DNA vaccines for autoimmune diseases and allograft rejection, Recent Pat. DNA Gene Seq., 4, 122, 10.2174/187221510793205700

Ratsimandresy, 2011, Active immunization against IL-23p19 improves experimental arthritis, Vaccine, 29, 9329, 10.1016/j.vaccine.2011.09.134

Cohen, 2008, Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: A twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial, Arthritis Rheum., 58, 1299, 10.1002/art.23417

Takeuchi, 2016, Effect of denosumab on Japanese patients with rheumatoid arthritis: A dose-response study of AMG 162 (Denosumab) in patients with rheumatoid arthritis on methotrexate to validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre, randomised, double-blind, placebo-controlled, phase II clinical trial, Ann. Rheum. Dis., 75, 983, 10.1136/annrheumdis-2015-208052

Feng, 2014, Therapeutic effects of PADRE-BAFF autovaccine on rat adjuvant arthritis, BioMed Res. Int., 2014, 854954, 10.1155/2014/854954

Mould, 2008, Prophylactic but not therapeutic activity of a monoclonal antibody that neutralizes the binding of VEGF-B to VEGFR-1 in a murine collagen-induced arthritis model, Rheumatology (Oxford), 47, 263, 10.1093/rheumatology/kem369

Rosenthal, 2015, Rheumatoid arthritis vaccine therapies: Perspectives and lessons from therapeutic ligand epitope antigen presentation system vaccines for models of rheumatoid arthritis, Expert Rev. Vaccines, 14, 891, 10.1586/14760584.2015.1026330

Chiu, 2017, Denosumab: Targeting the RANKL pathway to treat rheumatoid arthritis, Expert Opin Biol. Ther., 17, 119, 10.1080/14712598.2017.1263614

Malemud, 2015, Vaccine development for rheumatoid arthritis, Glob. Vaccines Immunol., 1, 2, 10.15761/GVI.1000102

Nandakumar, 2005, Efficient promotion of collagen antibody induced arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both collagen induced arthritis and rheumatoid arthritis, J. Immunol. Methods, 304, 126, 10.1016/j.jim.2005.06.017

Hasselberg, 2009, Role of CTA1R7K-COL-DD as a novel therapeutic mucosal tolerance-inducing vector for treatment of collagen-induced arthritis, Arthritis Rheum., 60, 1672, 10.1002/art.24566

Zimmerman, 2010, CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model, Int. Immunopharmacol., 10, 412, 10.1016/j.intimp.2009.12.016

Dzhambazov, 2006, Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules, J. Immunol., 176, 1525, 10.4049/jimmunol.176.3.1525

Kochetkova, 2008, Vaccination without autoantigen protects against collagen II-induced arthritis via immune deviation and regulatory T cells, J. Immunol., 181, 2741, 10.4049/jimmunol.181.4.2741

Luross, 2002, Escherichia coli heat-labile enterotoxin B subunit prevents autoimmune arthritis through induction of regulatory CD4+ T cells, Arthritis Rheum., 46, 1671, 10.1002/art.10328