Autoantibody and environmental damage to the brain

Las anormalidades de comportamiento y disfunciones cognitivas pueden presentarse en pacientes con enfermedades autoinmunes. Estos síntomas pueden fluctuar de leves hasta eventos potencialmente mortales. En su gran mayoría los mecanismos responsables de estas manifestaciones neuropsiquiatricas siguen...

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Autor Principal: Arango, María-Teresa
Otros Autores: Shoenfeld, Yehuda
Formato: Tesis de doctorado (Doctoral Thesis)
Lenguaje:Inglés (English)
Publicado: Universidad del Rosario 2016
Materias:
VPH
SLE
HPV
Acceso en línea:http://repository.urosario.edu.co/handle/10336/12875
id ir-10336-12875
recordtype dspace
institution EdocUR - Universidad del Rosario
collection DSpace
language Inglés (English)
topic Tejido Cerebral
Lupus eritematoso sistémico
Narcolepsia
Autoanticuerpos
Vacunas
VPH
Fisiología humana
Cerebro
Brain
Autoantibodies
SLE
Narcolepsy
Vaccines
HPV
Lupus Eritematoso Sistémico
Narcolepsia
Autoanticuerpos
Papillomavirus Humano
Tesis y disertaciones académicas
spellingShingle Tejido Cerebral
Lupus eritematoso sistémico
Narcolepsia
Autoanticuerpos
Vacunas
VPH
Fisiología humana
Cerebro
Brain
Autoantibodies
SLE
Narcolepsy
Vaccines
HPV
Lupus Eritematoso Sistémico
Narcolepsia
Autoanticuerpos
Papillomavirus Humano
Tesis y disertaciones académicas
Arango, María-Teresa
Autoantibody and environmental damage to the brain
description Las anormalidades de comportamiento y disfunciones cognitivas pueden presentarse en pacientes con enfermedades autoinmunes. Estos síntomas pueden fluctuar de leves hasta eventos potencialmente mortales. En su gran mayoría los mecanismos responsables de estas manifestaciones neuropsiquiatricas siguen siendo desconocidas, sin embargo se han identificado varias vías patogénicas. Por ejemplo; neurotoxicidad mediada por anticuerpos, vasculopatía inducida por anticuerpos anti-fosfolípidos, neurotoxicidad inducida por citoquinas, así como factores externos que incluyen sustancias tóxicas y medicamentos. Para poder investigar algunos de estos mecanismos, evaluamos el efecto de auto-anticuerpos relacionados con el lupus eritematoso sistémico neuropsiquiátrico en modelos animales (Anticuerpo idiotípico 16/6 y el anticuerpo anti-ribosoma P) y narcolepsia (empleando IgG de pacientes narcolépticos), así como el efecto de la vacuna del virus del papiloma humano en ratones. La inmunización pasiva por inyección intracerebro-ventricular de estos anticuerpos condujo a cambios histológicos, cognitivos y de comportamiento. En particular, los ratones inmunizados con el anticuerpo idiotípico 16/6 desarrollaron déficit cognitivo y los ratones inmunizados con el anticuerpo anti-ribosomal P desarrollaron depresión. Los ratones que recibieron IgG total de pacientes narcolépticos desarrollaron trastornos del sueño y cambios histológicos cerebrales consistentes con la enfermedad. Un análisis más profundo del papel del anticuerpo anti-ribosomal P humano reveló que reacciona de manera cruzada con la proteína neuronal “Gap43” interfiriendo con procesos celulares. Por otra parte, la inmunización con la vacuna del virus del papiloma humano causó la producción de anticuerpos contra componentes del cerebro. Adicionalmente, los ratones inmunizados con la vacuna, al igual que los inmunizados con su adyuvante desarrollaron deficiencia cognitiva y conductual, que fue mejorada con la suplementación alimenticia basada en fosfolípidos. En general, aquí se demuestra que anormalidades del comportamiento y disfunciones cognitiva pueden ser parte de la amplia gama de manifestaciones clínicas autoinmunes. Además, nuestros resultados sugieren que estas pueden ser causadas por daños colaterales debido a la desregulación inmune causada por autoinmunidad, así como por la vacunación. Adicionalmente, sugerimos que diferentes auto-anticuerpos causan diferentes síntomas basados en diferentes interacciones con el tejido cerebral.
author2 Shoenfeld, Yehuda
author_facet Shoenfeld, Yehuda
Arango, María-Teresa
format Tesis de doctorado (Doctoral Thesis)
author Arango, María-Teresa
author_sort Arango, María-Teresa
title Autoantibody and environmental damage to the brain
title_short Autoantibody and environmental damage to the brain
title_full Autoantibody and environmental damage to the brain
title_fullStr Autoantibody and environmental damage to the brain
title_full_unstemmed Autoantibody and environmental damage to the brain
title_sort autoantibody and environmental damage to the brain
publisher Universidad del Rosario
publishDate 2016
url http://repository.urosario.edu.co/handle/10336/12875
_version_ 1694382473523232768
spelling ir-10336-128752021-03-04T00:35:15Z Autoantibody and environmental damage to the brain Efecto de autoanticuerpos y factores ambientales en el cerebro Arango, María-Teresa Shoenfeld, Yehuda Blank, Miri Tejido Cerebral Lupus eritematoso sistémico Narcolepsia Autoanticuerpos Vacunas VPH Fisiología humana Cerebro Brain Autoantibodies SLE Narcolepsy Vaccines HPV Lupus Eritematoso Sistémico Narcolepsia Autoanticuerpos Papillomavirus Humano Tesis y disertaciones académicas Las anormalidades de comportamiento y disfunciones cognitivas pueden presentarse en pacientes con enfermedades autoinmunes. Estos síntomas pueden fluctuar de leves hasta eventos potencialmente mortales. En su gran mayoría los mecanismos responsables de estas manifestaciones neuropsiquiatricas siguen siendo desconocidas, sin embargo se han identificado varias vías patogénicas. Por ejemplo; neurotoxicidad mediada por anticuerpos, vasculopatía inducida por anticuerpos anti-fosfolípidos, neurotoxicidad inducida por citoquinas, así como factores externos que incluyen sustancias tóxicas y medicamentos. Para poder investigar algunos de estos mecanismos, evaluamos el efecto de auto-anticuerpos relacionados con el lupus eritematoso sistémico neuropsiquiátrico en modelos animales (Anticuerpo idiotípico 16/6 y el anticuerpo anti-ribosoma P) y narcolepsia (empleando IgG de pacientes narcolépticos), así como el efecto de la vacuna del virus del papiloma humano en ratones. La inmunización pasiva por inyección intracerebro-ventricular de estos anticuerpos condujo a cambios histológicos, cognitivos y de comportamiento. En particular, los ratones inmunizados con el anticuerpo idiotípico 16/6 desarrollaron déficit cognitivo y los ratones inmunizados con el anticuerpo anti-ribosomal P desarrollaron depresión. Los ratones que recibieron IgG total de pacientes narcolépticos desarrollaron trastornos del sueño y cambios histológicos cerebrales consistentes con la enfermedad. Un análisis más profundo del papel del anticuerpo anti-ribosomal P humano reveló que reacciona de manera cruzada con la proteína neuronal “Gap43” interfiriendo con procesos celulares. Por otra parte, la inmunización con la vacuna del virus del papiloma humano causó la producción de anticuerpos contra componentes del cerebro. Adicionalmente, los ratones inmunizados con la vacuna, al igual que los inmunizados con su adyuvante desarrollaron deficiencia cognitiva y conductual, que fue mejorada con la suplementación alimenticia basada en fosfolípidos. En general, aquí se demuestra que anormalidades del comportamiento y disfunciones cognitiva pueden ser parte de la amplia gama de manifestaciones clínicas autoinmunes. Además, nuestros resultados sugieren que estas pueden ser causadas por daños colaterales debido a la desregulación inmune causada por autoinmunidad, así como por la vacunación. Adicionalmente, sugerimos que diferentes auto-anticuerpos causan diferentes síntomas basados en diferentes interacciones con el tejido cerebral. Behavioral abnormalities and cognitive dysfunction may be present in patients with autoimmune diseases. The mechanisms that responsible for these neuropsychiatric manifestations are still largely unknown, however several pathogenic pathways have been identified such as antibody damage, cytokine-induced neurotoxicity, as well as external factors like toxics, and medications. To further investigate some of these mechanisms we evaluated the effect of autoantibodies in animal models of neuropsychiatric systemic lupus erythematosus and narcolepsy, and the effect of the human papillomavirus vaccine in naïve mice. Using the passive immunization method through intracerebro-ventricular injection of the antibodies, we demonstrated histological and behavioral changes. Mice immunized with 16/6 idiotypic antibodies developed cognitive impairments while those immunized with anti-ribosomal-P antibodies developed depression. The mice that received total IgG from narcoleptic patients developed sleep disturbances and brain histological changes. Further analyses of the role of the human anti-ribosomal-P autoantibody revealed that it can cross-react with the neuronal protein Gap43, interfering with cellular processes. Immunization with the human papillomavirus vaccine induced the production of brain antibodies. Moreover, the mice immunized with the vaccine or with its adjuvant developed cognitive and behavioral deficiencies, which were ameliorated with dietary phospholipid supplementation. Overall, herein we demonstrate that the behavioral and cognitive abnormalities can be part of the wide spectrum of clinical autoimmune manifestations. In addition, they can be caused by collateral damage due to the immune dysregulation caused by autoimmune conditions as well as by vaccination. We also suggest that different autoantibodies cause different symptoms based on different interactions with brain tissue. Colton Foundation Federico Foundation 2016-10-24 2017-02-06T15:22:20Z info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/acceptedVersion http://repository.urosario.edu.co/handle/10336/12875 eng http://creativecommons.org/licenses/by-nc-nd/2.5/co/ info:eu-repo/semantics/openAccess application/pdf Universidad del Rosario Doctorado en Ciencias Biomédicas Facultad de Ciencias Naturales y Matemáticas instname:Universidad del Rosario reponame:Repositorio Institucional EdocUR Strazielle N, Creidy R, Malcus C, Boucraut J, Ghersi-Egea JF. 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