Publication: Investigación traslacional en enfermedades infecciosas: análisis de la activación crónica del sistema inmune en la hepatitis C crónica y estudio de la actividad antiviral "in vitro" e "in vivo" de nanopartículas
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2018-02
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Universidad Complutense de Madrid
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Abstract
Durante la evolución de la hepatitis C crónica, la progresión de la fibrosis y la cirrosis hepática conlleva el desarrollo de complicaciones específicas de la enfermedad hepática avanzada. Se ha caracterizado el fenotipo celular por citometría de flujo multiparamétrica, junto al perfil inmunológico y el grado de activación/inflamación en plasma por ELISA multiplex, en pacientes coinfectados por VIH/VHC en distintos estadios clínicos de fibrosis y cirrosis en comparación con controles sanos y pacientes monoinfectados VIH. Los pacientes coinfectados VIH/VHC tuvieron mayores porcentajes de células T activadas y Treg, así como valores plasmáticos de biomarcadores de translocación bacteriana, inflamación, disfunción endotelial, coagulopatía, y citoquinas reguladoras del sistema inmune (Th1 y Th2) más altos. Por otra parte, la rigidez hepática (kPa) de estos pacientes coinfectados se asoció con disfunción del sistema inmune, encontrando una relación positiva entre el estadio de rigidez hepática y los marcadores de activación y senescencia del sistema inmune, translocación bacteriana, inflamación, disfunción endotelial y coagulopatía, observando una relación inversa con los valores plasmáticos de citoquinas relacionadas con la función inmune. Los pacientes coinfectados VIH/VHC con cirrosis avanzada (>40kPa) presentaron mayor nivel de disfunción del sistema inmune sobre el resto de pacientes, con porcentajes más altos de células T activadas, senescentes y Treg, junto a valores más elevados de marcadores de translocación bacteriana, inflamación, disfunción endotelial y coagulopatía. Estos pacientes también mostraron valores plasmáticos más bajos de citoquinas relacionadas con la función inmune y la proteína reguladora de inflamación IL-1RA con respecto a los individuos sanos y a los monoinfectados VIH. En conclusión, los pacientes coinfectados VIH/VHC presentaron una disfunción inmune directamente relacionada con el grado de rigidez hepática, siendo más acusada en los pacientes con cirrosis avanzada (>40kPa)...
During the evolution of chronic hepatitis C virus infection, progression of liver fibrosis and cirrhosis leads to the development of specific complications of advanced liver disease. In this study, cell phenotype, immunological profiles and degree of plasma activation/inflammation were characterized in HIV/HCV coinfected patients at different clinical stages of fibrosis and cirrhosis compared to healthy donors and HIV monoinfected patients using multiparametric flow cytometry and multiplex ELISA. HIV/HCV coinfected patients showed higher percentages of activated T-cells and Treg, as well as higher plasma levels of bacterial translocation, inflammation, endothelial dysfunction and coagulopathy biomarkers, and higher levels of Th1 and Th2 regulatory cytokines. On the other hand, hepatic stiffness (kPa) of HIV/HCV coinfected patients was associated with dysfunction of the immune system, defined by a positive relationship between the liver stiffness stage and several immunological parameters, such as cellular activation and senescence of immune cells, bacterial translocation, inflammation, endothelial dysfunction and coagulopathy. In contrast, an inverse relationship between hepatic stiffness (kPa) of HIV/HCV coinfected patients and plasma cytokine values related to immune function was observed. In addition, HIV/HCV coinfected patients with advanced cirrhosis (> 40kPa) showed higher level of immune cell dysfunction compared to the other study cohorts, and were characterized by higher percentages of activated, senescent and Treg T cells, along with higher values of bacterial translocation, inflammation, endothelial dysfunction and coagulopathy markers. These patients also showed lower plasma cytokine values related to immune function and the IL-1RA inflammatory regulatory protein compared to healthy donors and HIV monoinfected patients. In conclusion, HIV/HCV coinfected patients were characterized by an immune cell dysfunction which was directly related to the degree of hepatic stiffness, being more pronounced in patients with advanced cirrhosis >40kPa)...
During the evolution of chronic hepatitis C virus infection, progression of liver fibrosis and cirrhosis leads to the development of specific complications of advanced liver disease. In this study, cell phenotype, immunological profiles and degree of plasma activation/inflammation were characterized in HIV/HCV coinfected patients at different clinical stages of fibrosis and cirrhosis compared to healthy donors and HIV monoinfected patients using multiparametric flow cytometry and multiplex ELISA. HIV/HCV coinfected patients showed higher percentages of activated T-cells and Treg, as well as higher plasma levels of bacterial translocation, inflammation, endothelial dysfunction and coagulopathy biomarkers, and higher levels of Th1 and Th2 regulatory cytokines. On the other hand, hepatic stiffness (kPa) of HIV/HCV coinfected patients was associated with dysfunction of the immune system, defined by a positive relationship between the liver stiffness stage and several immunological parameters, such as cellular activation and senescence of immune cells, bacterial translocation, inflammation, endothelial dysfunction and coagulopathy. In contrast, an inverse relationship between hepatic stiffness (kPa) of HIV/HCV coinfected patients and plasma cytokine values related to immune function was observed. In addition, HIV/HCV coinfected patients with advanced cirrhosis (> 40kPa) showed higher level of immune cell dysfunction compared to the other study cohorts, and were characterized by higher percentages of activated, senescent and Treg T cells, along with higher values of bacterial translocation, inflammation, endothelial dysfunction and coagulopathy markers. These patients also showed lower plasma cytokine values related to immune function and the IL-1RA inflammatory regulatory protein compared to healthy donors and HIV monoinfected patients. In conclusion, HIV/HCV coinfected patients were characterized by an immune cell dysfunction which was directly related to the degree of hepatic stiffness, being more pronounced in patients with advanced cirrhosis >40kPa)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Microbiología II, leída el 16-06-2017