Publication: Biomarcadores predictivos en esclerosis múltiple
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2018-03-20
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Universidad Complutense de Madrid
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Abstract
La esclerosis múltiple (EM) es una enfermedad autoinmune crónica del sistema nervioso central (SNC) en la que participan en distinto grado mecanismos de inflamación, desmielinización, daño axonal, neurodegeneración, gliosis y remielinización. La EM se clasifica en tres formas clínicas predominantes: remitenterecurrente (EMRR), primaria progresiva (EMPP) y secundaria progresiva (EMSP). A día de hoy, en ausencia de un biomarcador específico, el diagnóstico de EM suele retrasarse al requerir la aparición de un segundo brote clínico o una confirmación de diseminación en espacio y tiempo de las lesiones por técnicas de neuroimagen para poder confirmar el diagnóstico. Uno de los mayores retos actuales es identificar biomarcadores capaces de reconocer y predecir el curso de la enfermedad en el paciente individual, que podría permitir el uso de estrategias terapéuticas más personalizadas, sobre todo en el caso de pacientes con formas progresivas, para los que actualmente no hay terapia disponible. Basándonos en resultados previos que nos permitieron definir un panel de 12 analitos con capacidad diagnóstica y pronóstica, hemos llevado a cabo un estudio transversal al inicio de las manifestaciones neurológicas para validar la utilidad clínica del mismo. En el estudio se han identificado y validado una serie de biomarcadores con elevado poder diagnóstico y pronóstico, que proporcionan por un lado una herramienta de utilidad en la práctica clínica habitual, y por otro lado permiten explorar y conocer en mayor profundidad la fisiopatología de la enfermedad y las diferencias entre las fases progresivas y las predominantemente inflamatorias...
Multiple sclerosis (MS) is considered an immune-mediated disease of the central nervous system (CNS). Different mechanisms of inflammation-demyelination, axonal damage, neurodegeneration, gliosis and remyelination-repair combine together in various degrees. Thus, its clinical course varies greatly, as with the response to therapies, creating a unique clinical result for each patient. Even so, MS is predominantly classified into three clinical forms: relapsing-remitting MS (RRMS), primary progressive (PPMS) and secondary progressive (SPMS). To date, in the absence of a more specific biomarker, MS diagnosis and the start of treatment is often delayed after a second clinical relapse or after confirming neuroimage dissemination of lesions in space and time. Our particular efforts in the last years have been focused on the search of a constellation of few relevant biomarkers able to predict the clinical form of MS from a personalized approach and explain the physiopathological processes that are taking place, especially at the beginning of MS. In summary, this study has contributed to the identification and validation of novel biomarkers related with type I interferon (IFN) signaling pathways which may provide useful tools for the classification of the different clinical forms of MS and to explore the pathophysiological differences between the progressive and the recurrent-remitting phase of the disease...
Multiple sclerosis (MS) is considered an immune-mediated disease of the central nervous system (CNS). Different mechanisms of inflammation-demyelination, axonal damage, neurodegeneration, gliosis and remyelination-repair combine together in various degrees. Thus, its clinical course varies greatly, as with the response to therapies, creating a unique clinical result for each patient. Even so, MS is predominantly classified into three clinical forms: relapsing-remitting MS (RRMS), primary progressive (PPMS) and secondary progressive (SPMS). To date, in the absence of a more specific biomarker, MS diagnosis and the start of treatment is often delayed after a second clinical relapse or after confirming neuroimage dissemination of lesions in space and time. Our particular efforts in the last years have been focused on the search of a constellation of few relevant biomarkers able to predict the clinical form of MS from a personalized approach and explain the physiopathological processes that are taking place, especially at the beginning of MS. In summary, this study has contributed to the identification and validation of novel biomarkers related with type I interferon (IFN) signaling pathways which may provide useful tools for the classification of the different clinical forms of MS and to explore the pathophysiological differences between the progressive and the recurrent-remitting phase of the disease...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Microbiología I, leída el 10-05-2017