Avanços recentes na compreensão da patogênese da Artrite Reumatoide: insights e implicações terapêuticas
DOI:
https://doi.org/10.34119/bjhrv6n4-037Keywords:
Artrite Reumatoide, imunidade inata, imunidade adaptativa, DMARDS, terapêuticaAbstract
A artrite reumatoide (AR) é uma doença autoimune sistêmica que afeta cerca de 1% da população mundial. Caracterizada por inflamação sinovial crônica e erosões ósseas progressivas, a AR provoca deformidade articular e incapacidade funcional, prejudicando seriamente a qualidade de vida dos pacientes. A patogênese da AR é complexa e envolve uma interação dinâmica entre fatores genéticos, imunológicos e ambientais. Nesta revisão, analisamos aprofundadamente o papel da imunidade inata e adaptativa na patogênese da AR e exploramos os avanços recentes na terapêutica da doença, com destaque para os medicamentos modificadores da doença (DMARDs), tanto biológicos quanto sintéticos. Discutimos também as perspectivas futuras para a pesquisa em AR e o desenvolvimento de terapias, com o objetivo de identificar as áreas de pesquisa mais promissoras e as lacunas ainda presentes no nosso entendimento.References
BAKER, P.N.; VAN DER MEULEN, J.H.; LEWINSON, R.; GREGORY, W. The role of pain and function in determining patient satisfaction after total knee replacement. The Journal of Bone and Joint Surgery, v. 89, n. 7, p. 893-900, 2007.
BREEDVELD, F.C.; WEISMAN, M.H.; KAVANAUGH, A.F.; et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis & Rheumatism, v. 54, n. 1, p. 26-37, 2006.
BUGATTI, S.; MANZO, A.; MONTECUCCO, C. B cells in rheumatoid arthritis. Autoimmun Rev, v. 7, n. 2, p. 137-142, 2007.
BURMESTER, G.R.; KREMER, J.M.; VAN DEN BOSCH, F.; et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. The Lancet, v. 391, n. 10139, p. 2503-2512, 2018.
BRENNAN, F. M.; MCINNES, I. B. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest, v. 118, n. 11, p. 3537-3545, 2008.
DALBETH, N.; CALLAN, M. F. A subset of natural killer cells is greatly expanded within inflamed joints. Arthritis Rheum, v. 46, n. 7, p. 1763-1772, 2002.
EDWARDS, J. C. et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med, v. 350, n. 25, p. 2572-2581, 2004.
FELDMANN, M.; MAINI, R.N. Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annual Review of Immunology, v. 19, p. 163-196, 2001.
FIRESTEIN, G. S. Evolving concepts of rheumatoid arthritis. Nature, v. 423, n. 6937, p. 356-361, 2003.
FLEISCHMANN, R. et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med, v. 367, n. 6, p. 495-507, 2012.
GIERUT, A.; PERLMAN, H.; POPE, R. M. Innate immunity and rheumatoid arthritis. Rheum Dis Clin North Am, v. 36, n. 2, p. 271-296, 2010.
GØTZSCHE, P. C.; JOHANSEN, H. K. Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Cochrane Database Syst Rev, n. 1, CD000189, 2004.
HAMMOND, A.; YOUNG, A.; KIDD, L. The impact of a nurse-led clinic on self-management and satisfaction in rheumatoid arthritis. Arthritis Care & Research, v. 45, n. 3, p. 228-233, 2001.
HOLERS, V. M. Complement and its receptors: new insights into human disease. Annu Rev Immunol, v. 32, p. 433-459, 2014.
HUANG, Q. Q.; POPE, R. M. The role of toll-like receptors in rheumatoid arthritis. Curr Rheumatol Rep, v. 11, n. 5, p. 357-364, 2009.
JOOSTEN, L. A. et al. Toll-like receptors and chronic inflammation in rheumatic diseases: new developments. Nat Rev Rheumatol, v. 12, n. 6, p. 344-357, 2016.
KLARESKOG, L.; CATRINA, A. I. Presentation of self-antigens by dendritic cells in the lung and skin leads to activation of autoreactive T cells and autoimmunity. Nat Rev Immunol, v. 18, n. 9, p. 643-655, 2018.
KREMER, J. M. et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med, v. 349, n. 20, p. 1907-1915, 2003.
MANZO, A.; PAOLETTI, S.; CARBONE, T.; et al. Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. European Journal of Immunology, v. 45, n. 5, p. 1347-1359, 2015.
MCINNES, I. B.; SCHETT, G. Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet, v. 389, n. 10086, p. 2328-2337, 2017.
MEASE, P. J. et al. Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med, v. 373, n. 14, p. 1329-1339, 2015.
NEMETH, T.; MOCSAI, A.; LOWELL, C.A. Neutrophils in animal models of autoimmune disease. Seminars in Immunology, v. 28, n. 2, p. 174-186, 2016.
PARK, J.S.; KWOK, S.K.; LIM, M.A.; et al. STA-21, a promising STAT-3 inhibitor that reciprocally regulates Th17 and Treg cells, inhibits osteoclastogenesis in mice and humans and alleviates autoimmune inflammation in an experimental model of rheumatoid arthritis. Arthritis & Rheumatology, v. 66, n. 4, p. 918-929, 2014.
SICA, G. L. et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity, v. 18, n. 6, p. 849-861, 2003.
SINGH, J.A.; SAAG, K.G.; BRIDGES, S.L.; et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis & Rheumatology, v. 68, n. 1, p. 1-26, 2016.
SINGH, J.A.; GUYATT, G.; OGDIE, A.; et al. Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Arthritis & Rheumatology, v. 71, n. 1, p. 5-32, 2019.
SAKAGUCHI, N. et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature, v. 426, n. 6965, p. 454-460, 2003.
SMOLEN, J. S.; ALETAHA, D. Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheumatol, v. 11, n. 5, p. 276-289, 2015.
SMOLEN, J.S.; ALETAHA, D.; MCINNES, I.B. Rheumatoid arthritis. The Lancet, v. 388, n. 10055, p. 2023-2038, 2016.
TAKEMURA, S. et al. Lymphoid neogenesis in rheumatoid synovitis. J Immunol, v. 167, n. 2, p. 1072-1080, 2001.
TAKEUCHI, O.; AKIRA, S. Pattern recognition receptors and inflammation. Cell, v. 140, n. 6, p. 805-820, 2010.
TAYLOR, P. C. et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med, v. 376, n. 7, p. 652-662, 2017.
VLIET Vlieland, T. P.; VAN DEN ENDE, C. H. Nonpharmacological treatment of rheumatoid arthritis. Curr Opin Rheumatol, v. 23, n. 3, p. 259-264, 2011.
WEYAND, C. M.; GORONZY, J. J. Immunometabolism in early and late stages of rheumatoid arthritis. Nat Rev Rheumatol, v. 13, n. 5, p. 291-301, 2017.
WRIGHT, H. L. et al. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford), v. 49, n. 9, p. 1618-1631, 2010.
WRIGHT, H. L.; MOOTS, R. J.; EDWARDS, S. W. The multifactorial role of neutrophils in rheumatoid arthritis. Nat Rev Rheumatol, v. 10, n. 10, p. 593-601, 2014.
YOKOTA, S.; IMAGAWA, T.; MURATA, T.; et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. The Lancet, v. 371, n. 9617, p. 998-1006, 2008.
