2016, Número 2
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Rev Cub de Reu 2016; 18 (2)
Leptina y artritis reumatoide, influencia de esta adipocina en la enfermedad
Batún GJAJ, Salas MM
Idioma: Español
Referencias bibliográficas: 82
Paginas: 129-141
Archivo PDF: 578.81 Kb.
RESUMEN
La artritis reumatoide es una enfermedad autoinmune inflamatoria, en cuya fisiopatología participan tanto factores ambientales como genéticos, teniendo como principales citocinas involucradas la interleucina 1, interleucina 6 y el factor de necrosis tumoral. Los pacientes con artritis reumatoide tienen hasta 2 a 3 veces mayor riesgo cardiovascular que la población en general, este riesgo es equiparable al de los pacientes con diabetes mellitus. Este aumento en la morbilidad cardiovascular se explica tanto por una mayor prevalencia de los factores de riesgo tradicionales, como por factores de riesgo no tradicionales. La obesidad o el exceso de tejido adiposo es un factor de riesgo que puede influir en el aumento del riesgo cardiovascular, esto debido a una mala regulación metabólica, aumento de la hipertensión arterial, dislipidemia, ácidos grasos libres circulantes y a la producción de citocinas. Últimamente ha surgido un amplío interés en estudiar la relación entre la artritis reumatoide y las adipocinas, sin embargo los resultados han sido heterogéneos, debido a la poca homogeneidad en los grupos de estudio. El objetivo de la siguiente revisión es hablar acerca de la influencia que tiene la leptina en la artritis reumatoide, en su fisiopatología, en la actividad de la enfermedad y en el aumento del riesgo cardiovascular.
REFERENCIAS (EN ESTE ARTÍCULO)
Méndez C, Andreu J, García B, Sangüesa C. Artritis reumatoide (II). Medicine. 2013; 11 (30): 1850-5.
Scott D, Wolfe F, Huizinga T. Rheumatoid arthritis. Lancet. 2010; 376 (9746):1094-108.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372: 425-32.
MacDougald O, Hwang C, Fan H, Lane M. Regulated expression of the obese gene product (leptin) in white adipose tissue and 3T3-L1 adipocytes. Proc Natl Acad Sci USA. 1995; 92: 9034-7.
Cannon B, Nedergaard J. Brown adipose tissue: Function and physiological significance. Physiol Rev. 2004; 84:277-359.
Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005; 115: 911-9.
Krysiak R, Handzlik G, Okopien B. The role of adipokines in connective tissue diseases. Eur J Nutr. 2012; 51 (5): 513-28.
Toussirot E, Streit G, Wendling D. The contribution of adipose tissue and adipokines to inflammation in joint diseases. Curr Med Chem. 2007; 14 (10): 1095-100.
Otero M, Lago R, Gómez R, Dieguez C, Lago F, Gómez J, et al. Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatology (Oxford). 2006; 45: 944-50.
Zhang F, Basinski M, Beals J, Briggs S, Churgay L, Clawson D, et al. Crystal structure of the obese protein leptin-E100. Nature. 1997; 387: 206-9.
Tian G, Liang J, Wang Z, Zhou D. Emerging role of leptin in rheumatoid arthritis. Clin Exp Immunol. 2014; 177 (3): 557-70.
Iikuni N, Lam Q, Lu L, Matarese G, La Cava A. Leptin and inflammation. Curr Immunol Rev. 2008; 4 (2): 70-9.
Tartaglia L, Dembski M, Weng X, Deng N, Culpepper J, Richards G, et al. Identification and expression cloning of a leptin receptor OB-R. Cell. 1995; 83: 1263-71.
Chen H, Charlat O, Tartaglia L, Woolf E, Weng X, Ellis S, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell. 1996; 84: 491-495.
Denver R, Bonett R, Boorse G. Evolution of leptin structure and function. Neuroendocrinology. 2011; 94 (1): 21-38.
Mackey N, Petri W. Leptin and mucosal immunity. Mucosal Immunol. 2012; 5: 472-9.
Wrann C, Laue T, Hübner L, Kuhlmann S, Jacobs S, Goudeva L, et al. Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions. Am J Physiol Endocrinol Metab. 2012; 302 (1):108-16.
Cottrell E, Mercer J. Leptin receptors. Handb Exp Pharmacol. 2012; (209): 3-21.
O’Shea J, Holland S, Staudt L. JAKs and STATs in Immunity, Immunodeficiency and Cancer. N Engl J Med. 2013; 368: 161-70.
Frühbeck G. Intracellular signalling pathways activated by leptin. Biochem J. 2006; 393: 7-20.
Gautron L, Elmquist J. Sixteen years and counting: an update on leptin in energy balance. J Clin Invest. 2011; 121 (6): 2087-93.
Botella C, Barbancho L, González V, Varela D. Leptina: implicaciones fisiológicas y clínicas. An Med Interna. 2001; 18 (3): 152-160.
MacGregor A, Snieder H, Rigby A, Koskenvuo M, Kaprio J, Aho K, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 2000; 43: 30-7.
Olivier J, Worthington J, Silman A. Genetic epidemiology of rheumatoid arthritis. Curr Opin Rheumatol. 2006; 18: 141-6
Plenge R, Cotsapas C, Davies L, Price A, de Bakker P, Maller J, et al. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet. 2007; 39: 1477-82.
Kallberg H, Padyukov L, Plenge R, Ronnelid J, Gregersen P, Van der Helm A, et al. Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet. 2007; 80: 867-75.
Begovich A, Carlton V, Honigberg L, Schrodi S, Chokkalingam A, Alexander H, et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet. 2004; 75 (2): 330-337.
Lee A, Li W, Liew A, Bombardier C, Weisman M, Massarotti E, et al. The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status. Genes Immun. 2005; 6 (2): 129-133.
Kurreeman F, Padyukov L, Marques R, Schrodi S, Seddighzadeh M, Stoeken G, et al. A candidate
gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. PLoS Med. 2007; 4 (9): e278.
Plenge R, Seielstad M, Padyukov L, Lee A, Remmers E, Ding B, et al. TRAF1-C5 as a risk locus for rheumatoid arthritis-a genomewide study. N Engl J Med. 2007; 357 (12): 1199-209.
Müller U, Nishioka K. P53 in rheumatoid arthritis: friend or foe?. Arthritis Res. 2000; 2 (3): 175-8
Kamphuis S, Kuis W, de Jager W, Teklenburg G, Massa M, Gordon G, et al. Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis. Lancet. 2005; 366: 50-6.
Lundberg K, Wegner N, Yucel T, Venables P. Periodontitis in RA-the citrullinated enolase connection. Nat Rev Rheumatol. 2010; 6: 727-30.
Wegner N, Wait R, Sroka A, Eick S, Nguyen K, Lundberg K, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 2010; 62 (9): 2662-72.
Szekanecz Z, Pakozdi A, Szentpetery A, Besenyei T, Koch A. Chemokines and angiogenesis in rheumatoid arthritis. Front Biosci (Elite Ed). 2009; 1: 44-51.
Polzer K, Baeten D, Soleiman A, Distler J, Gerlag D, Tak P, et al. Tumour necrosis factor blockade increases lymphangiogenesis in murine and human arthritic joints. Ann Rheum Dis. 2008; 67 (11):1610-6.
Panayi G. Even though T-cell-directed trials have been of limited success, is there reason for optimism?. Nat Clin Pract Rheumatol. 2006; 2: 58-9.
Lebre M, Jongbloed S, Tas S, Smeets T, McInnes I, Tak P. Rheumatoid arthritis synovium contains two subsets of CD83-DC-LAMP-dendritic cells with distinct cytokine profiles. Am J Pathol. 2008; 172 (4): 940-50.
Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, et al. Th17 funtions as an osteoclastogenic helper Tcell subset that links Tcell activation and bone destruction. J Exp Med. 2006; 203: 2673-82.
Lubberts E, Koenders M, Van den Berg W. The role of T cell interleukin-17 in conducting destructive arthritis: Lessons from animal models. Arthritis Res Ther. 2005; 7: 29-37.
Hamilton J, Tak P. The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases. Arthritis Rheum. 2009; 60 (5); 1210-22.
McInnes I, Schett G. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med. 2011; 365: 2205-19.
Feldmann M, Maini S. Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol Rev. 2008; 223:7-19
Matarese G, Moschos S, Mantzoros C. Leptin in immunology. J Immunol. 2005; 174 (11): 3137-42.
Faggioni R, Feingold K, Grunfeld C. Leptin regulation of the immune response and the immunodeficiency of malnutrition. Faseb J. 2001; 15: 2565-71.
Howard J, Lord G, Matarese G, Vendetti S, Ghatei M, Ritter M, et al. Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest. 1999; 104: 1051-9.
Gómez R, Conde J, Gómez J, Lago F, Gualillo O. Las adipocinas: mediadores emergentes de la respuesta inmune y de la inflamación. Reumatol Clin. 2009; 5: 6-12.
Oral E, Javor E, Ding L, Uzel G, Cochran E, Young J, et al. Leptin replacement therapymodulates circulating lymphocyte subsets and cytokine responsiveness in severe lipodystrophy. J Clin Endocrinol Metab. 2006; 91 (2): 621-28.
Serrano A. Células colaboradoras (TH1, TH2, TH17) y reguladoras (Treg, TH3, NKT) en la artritis reumatoide. Reumatol Clin. 2009; 5: 1-5.
Deng J, Liu Y, Yang M, Wang S, Zhang M, Wang X, et al. Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response. Arthritis Rheum. 2012; 64 (11): 3564-73.
Zeng H, Chi H. The interplay between regulatory T cells andmetabolismin immune regulation. Oncoimmunology. 2013; 2 (11): e26586.
De Rosa V, Procaccini C, Calì G, Pirozzi G, Fontana S, Zappacosta S, et al. A key role of leptin in the control of regulatory T cell proliferation. Immunity. 2007; 26 (2): 241-55.
Tilg H, Moschen A. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006; 6: 772-83.
Otero M, Lago R, Lago F, Casanueva F, Dieguez C, Gómez J. Leptin, from fat to inflammation: Old questions and new insights. Febs Lett. 2005; 579 (2): 295-301.
Hekerman P, Zeidler J, Korfmacher S, Bamberg S, Knobelspies H, Zabeau L, et al. Leptin induces inflammation-related genes in RINm5F insulinoma cells. BMC Mol Biol. 2007; 8: 41
Otvos L, Shao W, Vanniasinghe A, Amon M, Holub M, Kovalszky I, et al. Toward understanding the role of leptin and leptin receptor antagonism in preclinical models of rheumatoid arthritis. Peptides. 2011; 32 (8): 1567-74.
Busso N, So A, Chobaz V, Morard C, Martinez E, Talabot D, et al. Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthriti. J Immunol. 2002; 168 (2): 875-82.
Popa C, Netea M, Radstake T, van Riel P, Barrera P, van der Meer J. Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis, Ann. Rheum. Dis. 2005; 64 (8): 1195-98.
Hizmetli S, Kisa M, Gokalp N, Bakici M. Are plasma and synovial fluid leptin levels correlated with disease activity in rheumatoid arthritis?. Rheumatol Int. 2007; 27 (4): 335-38.
Olama S, Senna M, Elarman M. Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol Int. 2012; 32 (3): 683-90.
Yoshino T, Kusunoki N, Tanaka N, Kaneko K, Kusunoki Y, Endo H, et al. Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis. Intern Med. 2011; 50 (4): 269-75.
Seven A, Güzel S, Aslan M, Hamuryudan V. Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis. Rheumatol Int. 2009; 29 (7): 743-7.
Xibillé D, Ortiz E, Bustos C, Sandoval M, Hernández S, Dominguez L, et al. Leptin and adiponectin as predictors of disease activity in rheumatoid arthritis. Clin Exp Rheumatol. 2015; 33(4): 471-7.
Kim K, Choi H, Ji H, Song R, Yang H, Lee S, et al. Serum adipokine levels in rheumatoid arthritis patients and their contributions to the resistance to treatment. Mol Med Rep. 2014; 9 (1): 255-60.
Engvall I, Tengstrand B, Brismar K, Hafström I. Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin : a randomized study over 21 months. Arthritis Res Ther. 2010; 12: R197.
Popa C, Netea M, de Graaf J, van den Hoogen F, Radstake T, Toenhake H, et al. Circulating leptinand adiponectin concentrations during tumor necrosis factor blockade in patientswith active rheumatoid arthritis. J Rheumatol. 2009; 36 (4): 724-30.
Hollan I, Meroni P, Ahearn J, Cohen J, Curran S, Goodyear C, et al. Cardiovascular disease in autoimmune rheumatic diseases. Autoimmun Rev. 2013; 12: 1004-15.
Skeoch S, Bruce I. Atherosclerosis in rheumatoid arthritis: is it all about inflammation?. Nat Rev Rheumatol. 2015; 11: 390-400
Raggi P. Epicardial Adipose Tissue as a Marker of Coronary Artery Disease Risk. J Am Coll Cardiol. 2013; 61(13): 1396-139
Correia M, Haynes W. Leptin, obesity and cardiovascular disease. Curr Opin Nephrol Hypertens. 2004; 13 (2): 215-23.
Parhami F, Tintut Y, Ballard A, Fogelman A, Demer L. Leptin enhances the calcification of vascular cells: artery wall as a target of leptin. Circ Res. 2001; 88 9: 954-60.
Singhal A, Farooqi I, Cole T, O'Rahilly S, Fewtrell M, Kattenhorn M, et al. Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease?. Circulation. 2002; 106 (15): 1919-24.
Söderberg S, Ahrιn B, Jansson H, Johnson O, Hallmans G, Asplund K, et al. Leptin is associated with increased risk of myocardial infarction. J Int Med. 1999; 246 4: 409-18.
Wallace A, McMahon A, Packard C, Kelly A, Pastor J, Gaw A et al. Plasma Leptin and the Risk of Cardiovascular Disease in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 2001; 104: 3052-6
Taneli F, Yegane S, Ulman C, Tikiz H, Bilge A, Ari Z, et al. Increased Serum Concentrations in Patients with Chronic Stable Angina Pectoris and ST-Elevated Myocardial Infarction. Angiology. 2006; 57: 267-72.
Wilson P, D'Agostino R, Sullivan L, Parise H, Kannel W. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002; 162: 1867-72.
Alvarez G, Ballard T, Beske S, Davy K. Subcutaneous obesity is not associated with sympathetic neural activation. Am J Physiol Heart Circ Physiol. 2004; 287: 414-8.
Haynes W. Role of leptin in obesity-related hypertension. Exp Physiol. 2005; 90: 683-8.
Allison M, Ix J, Morgan C, McClelland R, Rifkin D, Shimbo D, Criqui M, et al. Higher leptin is associated with hypertension: the Multi-Ethnic Study of Atherosclerosis. J Hum Hypertens. 2013; 27 (10): 617-22.
Barba G, Russo O, Siani A, Iacone R, Farinaro E, Gerardi M, et al. Plasma leptin and blood pressure in men: graded association independent of body mass and fat pattern. Obes Res. 2003; 11(1): 160-6.
Huby A, Otvos L J, Belin de Chantemèle E. Leptin Induces Hypertension and Endothelial Dysfunction via Aldosterone-Dependent Mechanisms in Obese Female Mice Hypertension.2016; HYPERTENSIONAHA. 115 .06642published online before print March 7 2016.