Publication: Interacción célula sinovial-fibrina como mecanismo patogénico y oportunidad terapéutica en artritis reumatoide
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2017-07-04
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Universidad Complutense de Madrid
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Abstract
La artritis reumatoide (AR) es una enfermedad inflamatoria crónica, progresiva e invalidante, mediada por mecanismos inmunes, que afecta al uno por ciento de la población mundial adulta. El tratamiento de la artritis reumatoide ha sufrido una revolución en las últimas dos décadas con la llegada de los agentes biológicos, diseñados a partir del mejor conocimiento de los mecanismos patológicos de la enfermedad. Sin embargo, éstos aún muestran una eficacia limitada, tanto en la prevención del daño articular como en el porcentaje de pacientes respondedores. Esta situación es el reflejo de la compleja y heterogénea patogénesis de la enfermedad. Por este motivo es necesaria una continua búsqueda de nuevas estrategias. La deposición de fibrina intraarticular en la enfermedad es un proceso aún poco explotado en la búsqueda de tratamientos. En base a los estudios existentes, se puede considerar que la deposición de fibrina ocurre en fases tempranas de la cascada patogénica y tiene un papel en el desarrollo de la sinovitis. Por ello, este proceso constituye una diana ideal en el desarrollo de nuevas terapias. El objetivo del presente trabajo consistió en describir el proceso y los mecanismos de activación desencadenados por la fibrina en las articulaciones y su contribución al desarrollo y progresión de la AR, con la finalidad de identificar posibles dianas terapéuticas dirigidas a estos mecanismos...
Rheumatoid arthritis (RA) is an invalidating, progressive and chronic inflammatory illness mediated by immune mechanisms, affecting around one percent of the adult population around the world. Its treatment has undergone a huge revolution in the past two decades with the incoming of biological therapies, which have been developed as a result of a better understanding of RA pathogenesis. However, these new drugs display a limited efficacy, both at slowing down joint damage and in number of responders. This reflects the complexity of the disease, as well as its heterogeneous pathogenesis. In consequence, there is a continuous need for searching new therapeutic strategies. The intra-articular fibrin deposition in RA is currently a yet little-explored process in the development of anti rheumatoid compounds. In the light of previous studies, fibrin deposition inside joints could take place at the earliest phases of the pathogenic sequence, and participate in the generation of synovitis. Considering these facts, fibrin clotting could account for an attractive targetable process in RA. The objective in this work was to describe the process of activation triggered by fibrin in rheumatoid joints, and its contribution to disease progression, aiming at identifying targetable checkpoints of potential clinical use...
Rheumatoid arthritis (RA) is an invalidating, progressive and chronic inflammatory illness mediated by immune mechanisms, affecting around one percent of the adult population around the world. Its treatment has undergone a huge revolution in the past two decades with the incoming of biological therapies, which have been developed as a result of a better understanding of RA pathogenesis. However, these new drugs display a limited efficacy, both at slowing down joint damage and in number of responders. This reflects the complexity of the disease, as well as its heterogeneous pathogenesis. In consequence, there is a continuous need for searching new therapeutic strategies. The intra-articular fibrin deposition in RA is currently a yet little-explored process in the development of anti rheumatoid compounds. In the light of previous studies, fibrin deposition inside joints could take place at the earliest phases of the pathogenic sequence, and participate in the generation of synovitis. Considering these facts, fibrin clotting could account for an attractive targetable process in RA. The objective in this work was to describe the process of activation triggered by fibrin in rheumatoid joints, and its contribution to disease progression, aiming at identifying targetable checkpoints of potential clinical use...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, leída el 22/09/2016