Esclerosis múltiple: aspectos inmunológicos actuales
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Esclerosis múltiple
Enfermedades del sistema nervioso central
Respuesta inmune adaptativa

Resumen

La esclerosis múltiple es la enfermedad inflamatoria, crónica y degenerativa más frecuente del sistema nervioso central y representa la primera causa de discapacidad en adultos jóvenes. En México, 11 a 20 de cada 100 000 habitantes padecen la enfermedad. Aún se desconocen las causas de su origen, pero se han formulado varias teorías: la interacción de factores ambientales, infecciosos virales y susceptibilidad genética e inmunológica propia de cada paciente, que inducen una respuesta autoinmune y promueven la degeneración neuronal/axonal. En esta revisión se analizan los principales componentes de la respuesta inmune y la neurodegeneración presentes en la esclerosis múltiple, así como la cascada inflamatoria asociada con la desmielinización. Los tratamientos disponibles tienen como objetivo principal modular los aspectos relacionados con la respuesta inmune adaptativa (células B y T). El reto terapéutico será la inducción de tolerancia inmune antígeno-específica, por ejemplo, mediante el uso de protocolos de tolerancia con péptidos, vacunas de ADN o nanopartículas. Las futuras terapias deberán dirigirse a controlar los componentes innatos del sistema inmune (microglías, macrófagos, astrocitos) y a promover la remielinización. Para optimizar el tratamiento será necesario un enfoque terapéutico combinado dirigido al control de los componentes inflamatorios y neurodegenerativos de la enfermedad y al monitoreo de biomarcadores.

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Referencias

Coyle PK. Multiple sclerosis in pregnancy. Continuum (Minneap Minn) 2014;20(1):42-59. DOI: http://dx.doi.org/10.1212/01.CON.0000443836.18131.c9

Cuevas C, Velázquez M, Núñez L, Skromne E, Árcega R, Barroso N, et al. Consenso mexicano para la esclerosis múltiple. Guía diagnóstica y terapéutica. Rev Mex Neuroci. 2007;8(2):155-162. Disponible en: http://www.medigraphic.com/pdfs/revmexneu/rmn-2007/rmn072j.pdf

Correale J, Abad P, Alvarenga R, et al. Manejo de la esclerosis múltiple recurrente-remitente en Latinoamérica: recomendaciones prácticas para la optimización del tratamiento. J Neurol Sci. 2014;339:196-206.

Popescu BFG, Lucchinetti CF. Pathology of demyelinating diseases. Ann Rev Pathol Mechanisms of Disease. 2012;7:185-217. DOI: http://dx.doi.org/10.1146/annurev-pathol-011811-132443

Trapp BD, Stys PK. Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurology. 2009;8(3):280-291. DOI: http://dx.doi.org/10.1016/S1474-4422(09)70043-2

Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med. 2006;354(9):942-955.

International Multiple Sclerosis Genetics Consortium; Wellcome Trust Case Control Consortium 2; Sawcer S, Hellenthal G, Pirinen M, Spencer CC, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;47(7359);6:214-219. DOI: http://dx.doi.org/10.1038/nature10251

Ebers GC. Environmental factors and multiple sclerosis. Lancet Neurol. 2008;7(3):268-277. DOI: http://dx.doi.org/10.1016/S1474-4422(08)70042-5

Salzer J, Hallmans G, Nystrom M, Stenlund H, Wadell G, Sundstrom P. Vitamin D as a protective factor in multiple sclerosis. Neurology. 2012;79(2):2140-2145. DOI: http://dx.doi.org/10.1212/WNL.0b013e3182752ea8

Hedstrom AK, Sundqvist E, Baarnhielm M, Nordin N, Hillert J, Kockum I, et al. Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis. Brain. 2011;134(Pt 3):653-664. DOI: http://dx.doi.org/10.1093/brain/awq371

Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308(5726):1314-1318. DOI: http://dx.doi.org/10.1126/science.1110647

Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell. 1995;80(5):695-705. DOI: http://dx.doi.org/10.1016/0092-8674(95)90348-8

Weissert R, Svenningsson A, Lobell A, de Graaf KL, Andersson R, Olsson T. Molecular and genetic requirements for prefer- ential recruitment of TCRBV8S2+ T cells in Lewis rat experimental autoimmune encephalomyelitis. J Immunol. 1998;160(2):681-690. Disponible en: http://www.jimmunol.org/content/160/2/681.long

Harkiolaki M, Holmes SL, Svendsen P, Gregersen JW, Jensen LT, McMahon R, et al. T cell- mediated autoimmune disease due to low-affinity cross-reactivity to common microbial peptides. Immunity. 2009;30(3):348-357. DOI: http://dx.doi.org/10.1016/j.immuni.2009.01.009

Haring JS, Pewe LL, Perlman S. Bystander CD8 T cell-mediated demyelination after viral infection of the central nervous system. J Immunol. 2002;169(3):1550-1555. DOI: https://doi.org/10.4049/jimmunol.169.3.1550

Ji Q, Perchellet A, Goverman JM. Viral infection triggers central nervous system autoimmunity via activation of CD8+ T cells expressing dual TCRs. Nat Immunol. 2010;11(7):628-634. DOI: http://dx.doi.org/10.1038/ni.1888

Weller RO, Engelhardt B, Phillips MJ. Lymphocyte targeting of the central nervous system: a review of afferent and efferent CNS- immune pathways. Brain Pathol. 1996;6(3):275-288. DOI: http://dx.doi.org/10.1111/j.1750-3639.1996.tb00855.x

Lauterbach H, Zuniga EI, Truong P, Oldstone MBA, McGavern DB. Adoptive immunotherapy induces CNS dendritic cell re- cruitment and antigen presentation during clearance of a persistent viral infection. J Exp Med. 2006;203(8):1963-1975. DOI: http://dx.doi.org/10.1084/jem.20060039

Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009;27:119-145. DOI: http://dx.doi.org/10.1146/annurev.immunol.021908.132528

Becher B, Prat A, Antel JP. Brain-immune connection: immuno-regulatory properties of CNS-resident cells. Glia. 2000;29(4):293-304.

Szabo SJ, Sullivan BM, Peng SL, Glimcher LH. Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol. 2003;21:713-758. DOI: http://dx.doi.org/10.1146/annurev.immunol.21.120601.140942

Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol. 2009;27:485-517. DOI: http://dx.doi.org/10.1146/annurev.immunol.021908.132710

Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med. 2009;361(9):888-898. DOI: http://dx.doi.org/10.1056/NEJMra0707449

Panitch HS, Hirsch RL, Haley AS, Johnson KP. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet. 1987;1(8538):893-895.

Panitch HS, Hirsch RL, Schindler J, Johnson KP. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology 1987;37(7):1097-1102.

Deisß A, Brecht I, Haarmann A, Buttmann M. Treating multiple sclerosis with monoclonal antibodies: a 2013 update. Expert Rev Neurother. 2013;13(3):313-335. DOI: http://dx.doi.org/10.1586/ern.13.17

Fernández Ó, Arnal-García C, Arroyo-González R, Brieva L, Calles-Hernández MC, Casanova-Estruch B, et al. Revisión de las novedades presentadas en el XXVIII Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (III). Rev Neurol. 2013;57(7):317-329.

Codarri L, Gyülvészi G, Tosevski V, Hesske L, Fontana A, Magnenat L, et al. RORgammat drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nature Immunol. 2011;12(6):560-567. DOI: http://dx.doi.org/10.1038/ni.2027

Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN. GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol. 2007;178(1):39-48. DOI: https://doi.org/10.4049/jimmunol.178.1.39

Peters A, Pitcher LA, Sullivan JM, Mitsdoerffer M, Acton SE, Franz B, et al. Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation. Immunity. 2011;35(6):986-996. DOI: http://dx.doi.org/10.1016/j.immuni.2011.10.015

Quintana FJ, Farez MF, Izquierdo G, Lucas M, Cohen IR, Weiner HL. Antigen microarrays identify CNS-produced autoantibodies in RRMS. Neurology. 2012;78(8):532-539. DOI: http://dx.doi.org/10.1212/WNL.0b013e318247f9f3

Babbe H, Roers A, Waisman A, Lassmann H, Goebels N, Hohlfeld R, Friese M, et al. Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J Exp Med. 2000;192(3):393-404. DOI: http://dx.doi.org/10.1084/jem.192.3.393

Booss J, Esiri MM, Tourtellotte WW, Mason DY. Immunohistological analysis of T lymphocyte subsets in the central nervous system in chronic progressive multiple sclerosis. J Neurol Sciences. 1983;62(1-3):219-232.

Hauser SL, Bhan AK, Gilles F, Kemp M, Kerr C, Weiner HL. Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions. Ann Neurol. 1986;19(6):578-587.

Melzer N, Meuth SG, Wiendl H. CD8+ T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability. FASEB J. 2009;23(11):3659-3673. DOI: http://dx.doi.org/10.1096/fj.09-136200

Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Bruck W. Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain. 2000;123(Pt 6):1174-1183.

Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Bruck W. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain. 2002;125(Pt 10):2202-2212.

Neumann H, Cavalie A, Jenne DE, Wekerle H. Induction of MHC class I genes in neurons. Science. 1995;269(5223):549-552. DOI: http://dx.doi.org/10.1126/science.7624779

Luessi F. Siffrin V, Zipp F. Neurodegeneration in multiple sclerosis: novel treatment strategies. Exp Rev Neurotherapeutics. 2012;12(9):1061-1076. DOI: http://dx.doi.org/10.1586/ern.12.59

Medana IM, Gallimore A, Oxenius A, Martinic MM, Wekerle H, Neumann H.. MHC class I-restricted killing of neurons by virus-specific CD8+ T lymphocytes is affected through the Fas/FasL, but not the perforin pathway. Eur J Immunol. 2000;30(12):3623-3633.

Giuliani F, Goodyer CG, Antel JP, Yong VW. Vulnerability of human neurons to T cell-mediated cytotoxicity. J Immunol. 2003;171(1):368-379. DOI: https://doi.org/10.4049/jimmunol.171.1.368

Baldwin RL, Stolowit, ML, Hood L, Wisnieski BJ. Structural changes of tumor necrosis factor alpha associated with membrane insertion and channel formation. Proc Natl Acad Sciences USA. 1996;93(3):1021-1026. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40023/

Kagan BL, Baldwin RL, Munoz D, Wisnieski BJ. Formation of ion-permeable channels by tumor necrosis factor-alpha. Science. 1992;255(5050):1427-1430.

Venters HD, Dantzer, Kelley KW. Tumor necrosis factor-alpha induces neuronal death by silencing survival signals generated by the type I insulin-like growth factor receptor. Ann New York Acad Sci. 2000;917:210-220. DOI: http://dx.doi.org/10.1111/j.1749-6632.2000.tb05385.x

Venters HD, Dantzer R, Kelley KW. A new concept in neurodegeneration: TNFalpha is a silencer of survival signals. Trends Neurosci. 2000;23(4):175-180. DOI: http://dx.doi.org/10.1016/S0166-2236(99)01533-7

Mizuno T, Zhang G, Takeuchi H, Kawanokuchi J, Wang J, Sonobe Y, et al. Interferon-gamma directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-gamma receptor and AMPA GluR1 receptor. FASEB J. 2008;22(6):1797-1806. DOI: http://dx.doi.org/10.1096/fj.07-099499.

Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A, Ghorayeb C, et al. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol. 2010;67(4):452-461. DOI: http://dx.doi.org/10.1002/ana.21939

Piccio L, Naismith RT, Trinkaus K, Klein RS, Parks BJ, Lyons JA, et al. Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis. Arch Neurol. 2010;67(6):707-714. DOI: http://dx.doi.org/10.1001/archneurol.2010.99

Yeste A, Quintana FJ. Antigen microarrays for the study of autoimmune diseases. Clin Chem. 2013;59(7):1036-1044. DOI: http://dx.doi.org/10.1373/clinchem.2012

Aslam M, Kalluri SR, Cepok S, Kraus V, Buck D, Srivastava R, et al. The antibody response to oligodendrocyte specific protein in multiple sclerosis. J Neuroimmunol. 2010;221/1-2):81-86. DOI: http://dx.doi.org/10.1016/j.jneuroim.2010.02.008

Chan A, Decard BF, Franke C, Grummel V, Zhou D, Schottstedt V, et al. Serum antibodies to conformational and linear epitopes of myelin oligodendrocyte glycoprotein are not elevated in the preclinical phase of multiple sclerosis. Multiple sclerosis. 2010;16(10):1189-1192. DOI: http://dx.doi.org/10.1177/1352458510376406

Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Ann Review Immunol. 2009;27:119-145. DOI: http://dx.doi.org/10.1146/annurev.immunol.021908.132528

Goldmann T, Prinz M. Role of microglia in CNS autoimmunity. Clin Dev Immunol. 2013;2013:208093. DOI: http://dx.doi.org/10.1155/2013/208093

Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M. Macrophage plasticity and polarization in tissue repair and remodelling. J Pathology. 2013;229(2):176-185. DOI: http://dx.doi.org/10.1002/path.4133

Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, et al. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nature Immunol. 2011;12:231-238. DOI: http://dx.doi.10.1038/ni.1990

Peterson JW, Bo L, Mork S, Chang A, Trapp BD. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurology. 2001;50(3):389-400.

Singh S, Metz I, Amor S, van der Valk P, Stadelmann C, Brück W. Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons. Acta Neuropathol. 2013;125(4):595-608. DOI: http://dx.doi.org/10.1007/s00401-013-1082-0

Diestel A, Aktas O, Hackel D, Häke I, Meier S, Raine CS, et al. Activation of microglial poly(ADP-ribose)-polymerase-1 by cholesterol breakdown products during neuroinflammation: A link between demyelination and neuronal damage. J Exp Med. 2003;198(11):1729-1740. DOI: http://dx.doi.org/10.1084/jem.20030975

Farez MF, Quintana FJ, Gandhi R, Izquierdo G, Lucas M, Weiner HL. Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nature Immunol. 2009;10(9):958-964. DOI: http://dx.doi.org/10.1038/ni.1775

Hanisch UK. Microglia as a source and target of cytokines. Glia. 2002;40(2):140-155. DOI: http://dx.doi.org/10.1002/glia.10161

Olson JK, Miller SD. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol. 2004;173(6):3916-3924. DOI: https://doi.org/10.4049/jimmunol.173.6.3916

Takeuchi H, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R, et al. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem. 2006;281(30):21362-21368. Disponible en: http://www.jbc.org/content/281/30/21362.long

Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119(1):7-35. DOI: http://dx.doi.org/10.1007/s00401-009-0619-8

Brosnan CF, Raine CS. The astrocyte in multiple sclerosis revisited. Glia. 2013;61(4):453-465. DOI: http://dx.doi.org/10.1002/glia.22443

Janeway CA, Travers P, Walport M, Shlomchik MJ. Immunobiology: The immune system in health and disease. NewYork, NY: Garland Science; 2001.

Mascanfroni ID, Yeste A, Vieira SM, Burns EJ, Patel B, Sloma I, et al. Interleukin-27 acts on dendritic cells to suppress the T-cell response and autoimmunity by inducing the expression of ENTPD1 (CD39). Nature Immunol. 2013;14(10):1054-1063. DOI: http://dx.doi.org/10.1038/ni.2695

Monif M, Burnstock G, Williams DA. Microglia: Proliferation and activation driven by the P2X7 receptor. See comment in PubMed Commons below. Int J Biochem Cell Biol. 2010;42(11):1753-1756. DOI: http://dx.doi.org/10.1016/j.biocel.2010.06.021

Matute C, Torre I, Pérez-Cerdá F, Pérez-Samartín A, Alberdi E, Etxebarria E, et al. P2X(7) receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis. J Neuroscience. 2007;27(35):9525-9533. DOI: https://doi.org/10.1523/JNEUROSCI.0579-07.2007

Basso AS, Frenkel D, Quintana FJ, Costa-Pinto FA, Petrovic-Stojkovic S, Puckett L, et al. Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Inv. 2008;118(4):1532-1543. DOI: http://dx.doi.org/10.1172/JCI33464

Mayo L, Quintana FJ, Weiner HL. The innate immune system in demyelinating disease. Immunol Rev. 2012;248(1):170-187. DOI: http://dx.doi.org/10.1111/j.1600-065X.2012.01135.x

Boulanger JJ, Messier C. From precursors to myelinating oligodendrocytes: Contribution of intrinsic and extrinsic factors to white matter plasticity in the adult brain. Neuroscience 2014;269C:343-366. DOI: http://dx.doi.org/10.1016/j.neuroscience.2014.03.063

Amit Bar-Or. Immunology of multiple sclerosis. Neurol Clin 2005;23(1):149-175, vii. DOI: http://dx.doi.org/10.1016/j.ncl.2004.11.001

Rothwell N, Loddick S. Immune and inflamatory responses in the nervous system. Second edition. Oxford, UK; Oxford Scholarship Online; 2002. p. 127-144. DOI: http://dx.doi.org/10.1093/acprof:oso/9780198509806.001.0001

Rose JW, Carlson NG. Pathogenesis of multiple sclerosis. Continiuum Lifelong Learning Neurol. 2007;13(5):35-62. DOI: http://dx.doi.org/10.1212/01.CON.0000293640.98116.18

Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000;343:938-952. DOI: 10.1056/NEJM200009283431307

Kurtzke JF. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452.

Gonsette RE. Oxidative stress and excitotoxicity. A therapeutic issue in multiple sclerosis. Mult Scler. 2008;14(1):22-34. Disponible en: http://journals.sagepub.com/doi/abs/10.1177/1352458507080111?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&

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