Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/22069 |
Resumo: | Human immunodeficiency virus (HIV) uncontrolled replication results in the Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) reduces morbidity and mortality but inflammation and immune activation remain. Two parameters are assessed in this thesis in HIV-positive individuals under ART and on viral suppression: the CD4/CD8 ratio and the activity of adenosine deaminase (ADA). CD4/CD8 and its relationships with comorbidities and aging were evaluated in a retrospective study with clinical and laboratory data from 352 HIV-positive individuals under ART. Despite the high prevalence of CD4/CD8 <1 (68%) and comorbidities (62%), no association was observed between them. The prevalence of comorbidities increased with aging, while the decrease in CD4/CD8 was associated only with neurocognitive diseases. ADA was investigated by studying the activity of ADA in serum and ecto-ADA in peripheral blood mononuclear cells (PBMCs) of 47 HIV-positive individuals and 71 controls, as well as serum parameters of oxidative stress. Compared to the control group, the HIV group showed increased serum ADA activity and reactive oxygen species (EROS) levels, and a reduction of E-ADA activity in PBMCs. The increase in serum ADA activity in the HIV group was associated with CD4/CD8<1 (66%) and elevated EROS levels, while the decrease in E-ADA in PBMCs was associated with the decrease in the CD4/CD8 ratio. A high prevalence of CD4/CD8<1 was observed in both studies and the activities of ADA were associated with changes in the CD4/CD8 ratio. Both markers indicate the permanence of immune dysfunction, regardless of the duration of treatment and the duration of viral suppression. |
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Manancial - Repositório Digital da UFSM |
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Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminaseImmune dysfunction in hiv-positive individuals under antiretroviral therapy: role of CD4/CD8 ratio and the activity of the enzyme adenosine deaminaseHIV (Vírus da Imunodeficiência Humana)TARVCD4/CD8Adenosina desaminaseAdenosine deaminaseCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAHuman immunodeficiency virus (HIV) uncontrolled replication results in the Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) reduces morbidity and mortality but inflammation and immune activation remain. Two parameters are assessed in this thesis in HIV-positive individuals under ART and on viral suppression: the CD4/CD8 ratio and the activity of adenosine deaminase (ADA). CD4/CD8 and its relationships with comorbidities and aging were evaluated in a retrospective study with clinical and laboratory data from 352 HIV-positive individuals under ART. Despite the high prevalence of CD4/CD8 <1 (68%) and comorbidities (62%), no association was observed between them. The prevalence of comorbidities increased with aging, while the decrease in CD4/CD8 was associated only with neurocognitive diseases. ADA was investigated by studying the activity of ADA in serum and ecto-ADA in peripheral blood mononuclear cells (PBMCs) of 47 HIV-positive individuals and 71 controls, as well as serum parameters of oxidative stress. Compared to the control group, the HIV group showed increased serum ADA activity and reactive oxygen species (EROS) levels, and a reduction of E-ADA activity in PBMCs. The increase in serum ADA activity in the HIV group was associated with CD4/CD8<1 (66%) and elevated EROS levels, while the decrease in E-ADA in PBMCs was associated with the decrease in the CD4/CD8 ratio. A high prevalence of CD4/CD8<1 was observed in both studies and the activities of ADA were associated with changes in the CD4/CD8 ratio. Both markers indicate the permanence of immune dysfunction, regardless of the duration of treatment and the duration of viral suppression.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA replicação descontrolada do vírus da imunodeficiência humana (HIV) resulta na Síndrome da Imunodeficiência Adquirida (AIDS). A terapia antirretroviral (TARV) reduz a morbidade e a mortalidade, mas a inflamação e ativação imune permanecem. Nessa tese, dois parâmetros são avaliados em indivíduos HIV positivos sob TARV em supressão viral: a razão CD4/CD8 e a atividade da adenosina desaminase (ADA). CD4/CD8 e sua relação com comorbidades e envelhecimento foi avaliada em um estudo retrospectivo com 352 indivíduos HIV positivos sob TARV. Apesar da alta prevalência de CD4/CD8 <1 (68%) e de comorbidades (62%), não foi observada associação entre elas. A prevalência de comorbidades aumentou com o envelhecimento, enquanto a diminuição de CD4/CD8 se mostrou associada somente a doenças neurocognitivas. A investigação da ADA foi feita através da análise da atividade da ADA no soro e da ecto-ADA em células mononucleares do sangue periférico (PBMCs) de 47 indivíduos HIV positivos e 71 controles, bem como parâmetros séricos de estresse oxidativo. O grupo HIV mostrou um aumento da atividade da ADA no soro e dos níveis de espécies reativas do oxigênio (EROS), e redução da atividade da E-ADA em PBMCs. O aumento da atividade da ADA no soro no grupo HIV se mostrou associado à CD4/CD8<1 (66%) e níveis elevados de EROS, enquanto a diminuição da E-ADA nas PBMCs acompanhou a queda na razão CD4/CD8. Uma prevalência alta de CD4/CD8<1 foi observada nos dois estudos, e a atividades da ADA se mostraram associadas à razão CD4/CD8. Os dois marcadores estudados demonstram a permanência da disfunção imune nos indivíduos HIV positivos em TARV, independentemente da duração do tratamento e do tempo de supressão viral nos indivíduos HIV positivos sob TARV.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasLeal, Daniela Bitencourt Rosahttp://lattes.cnpq.br/3639683273462361Schetinger, Maria Rosa ChitolinaMartínez, Ana Maria Barral deSpanevello, Roselia MariaBarbosa, Nilda Berenice de VargasCruz, Ivana Beatrice Mânica daPassos, Daniela Ferreira2021-08-25T22:55:56Z2021-08-25T22:55:56Z2021-03-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/22069porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-08-27T06:03:37Zoai:repositorio.ufsm.br:1/22069Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-08-27T06:03:37Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase Immune dysfunction in hiv-positive individuals under antiretroviral therapy: role of CD4/CD8 ratio and the activity of the enzyme adenosine deaminase |
title |
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase |
spellingShingle |
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase Passos, Daniela Ferreira HIV (Vírus da Imunodeficiência Humana) TARV CD4/CD8 Adenosina desaminase Adenosine deaminase CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase |
title_full |
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase |
title_fullStr |
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase |
title_full_unstemmed |
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase |
title_sort |
Disfunção imune em indivíduos HIV positivos sob terapia antirretroviral: papel da razão CD4/CD8 e da atividade da enzima adenosina desaminase |
author |
Passos, Daniela Ferreira |
author_facet |
Passos, Daniela Ferreira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Leal, Daniela Bitencourt Rosa http://lattes.cnpq.br/3639683273462361 Schetinger, Maria Rosa Chitolina Martínez, Ana Maria Barral de Spanevello, Roselia Maria Barbosa, Nilda Berenice de Vargas Cruz, Ivana Beatrice Mânica da |
dc.contributor.author.fl_str_mv |
Passos, Daniela Ferreira |
dc.subject.por.fl_str_mv |
HIV (Vírus da Imunodeficiência Humana) TARV CD4/CD8 Adenosina desaminase Adenosine deaminase CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
HIV (Vírus da Imunodeficiência Humana) TARV CD4/CD8 Adenosina desaminase Adenosine deaminase CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Human immunodeficiency virus (HIV) uncontrolled replication results in the Acquired Immunodeficiency Syndrome (AIDS). Antiretroviral therapy (ART) reduces morbidity and mortality but inflammation and immune activation remain. Two parameters are assessed in this thesis in HIV-positive individuals under ART and on viral suppression: the CD4/CD8 ratio and the activity of adenosine deaminase (ADA). CD4/CD8 and its relationships with comorbidities and aging were evaluated in a retrospective study with clinical and laboratory data from 352 HIV-positive individuals under ART. Despite the high prevalence of CD4/CD8 <1 (68%) and comorbidities (62%), no association was observed between them. The prevalence of comorbidities increased with aging, while the decrease in CD4/CD8 was associated only with neurocognitive diseases. ADA was investigated by studying the activity of ADA in serum and ecto-ADA in peripheral blood mononuclear cells (PBMCs) of 47 HIV-positive individuals and 71 controls, as well as serum parameters of oxidative stress. Compared to the control group, the HIV group showed increased serum ADA activity and reactive oxygen species (EROS) levels, and a reduction of E-ADA activity in PBMCs. The increase in serum ADA activity in the HIV group was associated with CD4/CD8<1 (66%) and elevated EROS levels, while the decrease in E-ADA in PBMCs was associated with the decrease in the CD4/CD8 ratio. A high prevalence of CD4/CD8<1 was observed in both studies and the activities of ADA were associated with changes in the CD4/CD8 ratio. Both markers indicate the permanence of immune dysfunction, regardless of the duration of treatment and the duration of viral suppression. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-25T22:55:56Z 2021-08-25T22:55:56Z 2021-03-31 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/22069 |
url |
http://repositorio.ufsm.br/handle/1/22069 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805922066742902784 |