Comparación de los perfiles de transcripción de pacientes con fiebre de dengue y fiebre hemorrágica por dengue que muestra diferencias en la respuesta inmunitaria y claves en la inmunopatogénesis

Natalia Houghton-Triviño, Katherine Martín, Kris Giaya, Jairo A. Rodríguez, Irene Bosch, Jaime E. Castellanos, .

Palabras clave: dengue, transcripción genética, análisis de micromatrices, fiebre hemorrágica del dengue, proteínas del sistema del complemento, citocinas

Resumen

Introducción. El dengue puede manifestarse como una enfermedad leve o evolucionar hasta una enfermedad grave, llamada fiebre hemorrágica por dengue, cuyos mecanismos de inmunopatogénesis no son claros.
Objetivo. Utilizar un análisis de microarreglos para identificar los genes de la respuesta inmunitaria diferencialmente expresados en niños colombianos con dengue leve y grave.
Materiales y métodos. Se evaluaron los cambios de la expresión génica de células mononucleares de sangre periférica de niños con fiebre de dengue y fiebre hemorrágica por dengue en fase aguda, mediante el microarreglo de Affymetrix HG-U133_Plus_2.
Resultados. Los pacientes con fiebre hemorrágica por dengue expresaron transcritos para interleucina 6, quimiocinas, complemento y pentraxina 3, al igual que inhibidores de la actividad de linfocitos (gen 3 de activación de linfocitos y catepsina L1). Un modelo de interacción desarrollado para estos genes mostró al factor tisular como central en la red generada. Por el contrario, los pacientes con fiebre de dengue expresaron inhibidores de la actividad de citocinas, complemento y leucotrienos [lactotransferrina, inhibidor peptidasa serpina del complemento C1, leucotrieno B (4-omega hidroxilasa 2)].
Conclusiones. Los resultados podrían indicar que durante la fiebre de dengue, los inhibidores de citocinas y del complemento logran controlar el daño al endotelio y el aumento de la permeabilidad vascular, mientras que, en los pacientes con fiebre hemorrágica por dengue, la disfunción de las células inmunitarias y la acción no regulada del complemento y de las citocinas, conducen a un estado de "hipercoagulacion" y daño endotelial. La identificación del papel patógeno de las moléculas encontradas podría contribuir a la interpretación de la patogenia y al desarrollo de fármacos terapéuticos.

 

 

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  • Natalia Houghton-Triviño Grupo de Virología, Universidad El Bosque, Bogotá, D.C., Colombia Grupo de Enfermedades Tropicales, Universidad Simón Bolívar, Barranquilla, Colombia
  • Katherine Martín Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA, USA
  • Kris Giaya Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA, USA
  • Jairo A. Rodríguez Grupo Parasitología y Medicina Tropical, Universidad Surcolombiana, Neiva, Colombia
  • Irene Bosch Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA, USA
  • Jaime E. Castellanos Grupo de Virología, Universidad El Bosque, Bogotá, D.C., Colombia

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Cómo citar
Houghton-Triviño, N., Martín, K., Giaya, K., Rodríguez, J. A., Bosch, I., & Castellanos, J. E. (2010). Comparación de los perfiles de transcripción de pacientes con fiebre de dengue y fiebre hemorrágica por dengue que muestra diferencias en la respuesta inmunitaria y claves en la inmunopatogénesis. Biomédica, 30(4), 587-97. https://doi.org/10.7705/biomedica.v30i4.297
Publicado
2010-12-01
Sección
Artículos originales