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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Tipo de recurso:
Fecha de publicación:
2016
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/12875
Acceso en línea:
https://doi.org/10.48713/10336_12875
http://repository.urosario.edu.co/handle/10336/12875
Palabra clave:
Tejido Cerebral
Lupus eritematoso sistémico
Narcolepsia
Autoanticuerpos
Vacunas
VPH
Fisiología humana
Lupus Eritematoso Sistémico
Narcolepsia
Autoanticuerpos
Papillomavirus Humano
Tesis y disertaciones académicas
Brain
Autoantibodies
SLE
Narcolepsy
Vaccines
HPV
Cerebro
Rights
License
Abierto (Texto completo)
id EDOCUR2_ac6630036489c102d6ecc8c770b77597
oai_identifier_str oai:repository.urosario.edu.co:10336/12875
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.spa.fl_str_mv Autoantibody and environmental damage to the brain
dc.title.TranslatedTitle.eng.fl_str_mv Efecto de autoanticuerpos y factores ambientales en el cerebro
title Autoantibody and environmental damage to the brain
spellingShingle Autoantibody and environmental damage to the brain
Tejido Cerebral
Lupus eritematoso sistémico
Narcolepsia
Autoanticuerpos
Vacunas
VPH
Fisiología humana
Lupus Eritematoso Sistémico
Narcolepsia
Autoanticuerpos
Papillomavirus Humano
Tesis y disertaciones académicas
Brain
Autoantibodies
SLE
Narcolepsy
Vaccines
HPV
Cerebro
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
dc.contributor.advisor.none.fl_str_mv Shoenfeld, Yehuda
Blank, Miri
dc.subject.spa.fl_str_mv Tejido Cerebral
Lupus eritematoso sistémico
Narcolepsia
Autoanticuerpos
Vacunas
VPH
topic Tejido Cerebral
Lupus eritematoso sistémico
Narcolepsia
Autoanticuerpos
Vacunas
VPH
Fisiología humana
Lupus Eritematoso Sistémico
Narcolepsia
Autoanticuerpos
Papillomavirus Humano
Tesis y disertaciones académicas
Brain
Autoantibodies
SLE
Narcolepsy
Vaccines
HPV
Cerebro
dc.subject.ddc.none.fl_str_mv Fisiología humana
dc.subject.decs.spa.fl_str_mv Lupus Eritematoso Sistémico
Narcolepsia
Autoanticuerpos
Papillomavirus Humano
Tesis y disertaciones académicas
dc.subject.keyword.eng.fl_str_mv Brain
Autoantibodies
SLE
Narcolepsy
Vaccines
HPV
dc.subject.lemb.spa.fl_str_mv Cerebro
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.
publishDate 2016
dc.date.created.none.fl_str_mv 2016-10-24
dc.date.issued.none.fl_str_mv 2016
dc.date.accessioned.none.fl_str_mv 2017-02-06T15:22:20Z
dc.date.available.none.fl_str_mv 2017-02-06T15:22:20Z
dc.type.eng.fl_str_mv doctoralThesis
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_db06
dc.type.spa.spa.fl_str_mv Tesis de doctorado
dc.identifier.doi.none.fl_str_mv https://doi.org/10.48713/10336_12875
dc.identifier.uri.none.fl_str_mv http://repository.urosario.edu.co/handle/10336/12875
url https://doi.org/10.48713/10336_12875
http://repository.urosario.edu.co/handle/10336/12875
dc.language.iso.none.fl_str_mv eng
language eng
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.acceso.spa.fl_str_mv Abierto (Texto completo)
dc.rights.cc.spa.fl_str_mv Atribución-NoComercial-SinDerivadas 2.5 Colombia
dc.rights.uri.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/2.5/co/
rights_invalid_str_mv Abierto (Texto completo)
Atribución-NoComercial-SinDerivadas 2.5 Colombia
http://creativecommons.org/licenses/by-nc-nd/2.5/co/
http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Universidad del Rosario
dc.publisher.department.spa.fl_str_mv Facultad de Ciencias Naturales y Matemáticas
dc.publisher.program.spa.fl_str_mv Doctorado en Ciencias Biomédicas
institution Universidad del Rosario
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spelling Shoenfeld, Yehuda30767258-89d1-4e0b-9ea6-2aa2d4659b8f-1Blank, Miri602e7c44-2fda-440b-ab6b-efd8b8213e7c-1Arango, María-TeresaDoctor en Ciencias Biomédicasc738ad51-5286-4f40-a6f7-52a6c04fbbdf-12017-02-06T15:22:20Z2017-02-06T15:22:20Z2016-10-242016Las 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 FoundationFederico Foundationapplication/pdfhttps://doi.org/10.48713/10336_12875 http://repository.urosario.edu.co/handle/10336/12875engUniversidad del RosarioFacultad de Ciencias Naturales y MatemáticasDoctorado en Ciencias BiomédicasAbierto (Texto completo)Atribución-NoComercial-SinDerivadas 2.5 ColombiaEL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DEL ROSARIO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. -------------------------------------- POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DEL ROSARIO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. 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