Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/xmlui/handle/11600/62166 https://doi.org/10.1007/s12035-020-02110-1 |
Resumo: | There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined Teff/Treg subsets both before and after ex vivo anti-CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 symptomatic remitted BD patients and 21 healthy controls and assessed human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of unstimulated CD3 + CD8 + CD71+ and CD4 + CD25 + FOXP3 and increased CD4 + CD25 + FOXP3 + CD152+ frequencies and with lowered stimulated frequencies of CD3 + CD8 + CD71+, CD4 + CD25 + FOXP3 + CD152+, and CD4 + CD25 + FOXP3 + GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3 + CD4 + CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4 + CD25 + FOXP+GARP T phenotypes. In conclusion, in BD patients, immune injuries, staging, and HCMV seropositivity interact and cause CIRS dysfunctions and exaggerated IRS responses, which play a key role in parainflammation and neuroaffective toxicity. HCMV seropositivity contributes to an immune-risk phenotype in BD. |
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Maes, MichaelNani, João Victor [UNIFESP]Noto, Cristiano [UNIFESP]Rizzo, LucasHayashi, Mirian A. F. [UNIFESP]Brietzke, Elisahttp://lattes.cnpq.br/55593093952321472021-10-29T17:13:07Z2021-10-29T17:13:07Z2020-09-11Molecular Neurobiology, Clifton, NJ, v. 58, n. 1, p. 229-242, Jan. 20211559-1182https://repositorio.unifesp.br/xmlui/handle/11600/62166https://doi.org/10.1007/s12035-020-02110-110.1007/s12035-020-02110-1There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined Teff/Treg subsets both before and after ex vivo anti-CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 symptomatic remitted BD patients and 21 healthy controls and assessed human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of unstimulated CD3 + CD8 + CD71+ and CD4 + CD25 + FOXP3 and increased CD4 + CD25 + FOXP3 + CD152+ frequencies and with lowered stimulated frequencies of CD3 + CD8 + CD71+, CD4 + CD25 + FOXP3 + CD152+, and CD4 + CD25 + FOXP3 + GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3 + CD4 + CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4 + CD25 + FOXP+GARP T phenotypes. In conclusion, in BD patients, immune injuries, staging, and HCMV seropositivity interact and cause CIRS dysfunctions and exaggerated IRS responses, which play a key role in parainflammation and neuroaffective toxicity. HCMV seropositivity contributes to an immune-risk phenotype in BD.p. 229-242engHumana PressMolecular NeurobiologyBipolar depressionCytokinesInflammationNeuroimmunomodulationPsychoneuroimmunologyStagingImpairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levelsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleClifton, NJinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPEscola Paulista de Medicina (EPM)FarmacologiaOutraFarmacologiaORIGINALMaes2021_Article_ImpairmentsInPeripheralBloodTE.pdfMaes2021_Article_ImpairmentsInPeripheralBloodTE.pdfapplication/pdf740292${dspace.ui.url}/bitstream/11600/62166/1/Maes2021_Article_ImpairmentsInPeripheralBloodTE.pdf5329658fb59227ea9893e0dfc59ea6f0MD51open accessLICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv |
Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels |
title |
Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels |
spellingShingle |
Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels Maes, Michael Bipolar depression Cytokines Inflammation Neuroimmunomodulation Psychoneuroimmunology Staging |
title_short |
Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels |
title_full |
Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels |
title_fullStr |
Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels |
title_full_unstemmed |
Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels |
title_sort |
Impairments in peripheral blood T effector and T regulatory lymphocytes in bipolar disorder are associated with staging of illness and anti-cytomegalovirus IgG levels |
author |
Maes, Michael |
author_facet |
Maes, Michael Nani, João Victor [UNIFESP] Noto, Cristiano [UNIFESP] Rizzo, Lucas Hayashi, Mirian A. F. [UNIFESP] Brietzke, Elisa |
author_role |
author |
author2 |
Nani, João Victor [UNIFESP] Noto, Cristiano [UNIFESP] Rizzo, Lucas Hayashi, Mirian A. F. [UNIFESP] Brietzke, Elisa |
author2_role |
author author author author author |
dc.contributor.authorLattes.pt_BR.fl_str_mv |
http://lattes.cnpq.br/5559309395232147 |
dc.contributor.author.fl_str_mv |
Maes, Michael Nani, João Victor [UNIFESP] Noto, Cristiano [UNIFESP] Rizzo, Lucas Hayashi, Mirian A. F. [UNIFESP] Brietzke, Elisa |
dc.subject.por.fl_str_mv |
Bipolar depression Cytokines Inflammation Neuroimmunomodulation Psychoneuroimmunology Staging |
topic |
Bipolar depression Cytokines Inflammation Neuroimmunomodulation Psychoneuroimmunology Staging |
description |
There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined Teff/Treg subsets both before and after ex vivo anti-CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 symptomatic remitted BD patients and 21 healthy controls and assessed human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of unstimulated CD3 + CD8 + CD71+ and CD4 + CD25 + FOXP3 and increased CD4 + CD25 + FOXP3 + CD152+ frequencies and with lowered stimulated frequencies of CD3 + CD8 + CD71+, CD4 + CD25 + FOXP3 + CD152+, and CD4 + CD25 + FOXP3 + GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3 + CD4 + CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4 + CD25 + FOXP+GARP T phenotypes. In conclusion, in BD patients, immune injuries, staging, and HCMV seropositivity interact and cause CIRS dysfunctions and exaggerated IRS responses, which play a key role in parainflammation and neuroaffective toxicity. HCMV seropositivity contributes to an immune-risk phenotype in BD. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-09-11 |
dc.date.accessioned.fl_str_mv |
2021-10-29T17:13:07Z |
dc.date.available.fl_str_mv |
2021-10-29T17:13:07Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Molecular Neurobiology, Clifton, NJ, v. 58, n. 1, p. 229-242, Jan. 2021 |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/xmlui/handle/11600/62166 https://doi.org/10.1007/s12035-020-02110-1 |
dc.identifier.issn.none.fl_str_mv |
1559-1182 |
dc.identifier.doi.none.fl_str_mv |
10.1007/s12035-020-02110-1 |
identifier_str_mv |
Molecular Neurobiology, Clifton, NJ, v. 58, n. 1, p. 229-242, Jan. 2021 1559-1182 10.1007/s12035-020-02110-1 |
url |
https://repositorio.unifesp.br/xmlui/handle/11600/62166 https://doi.org/10.1007/s12035-020-02110-1 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Molecular Neurobiology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
p. 229-242 |
dc.coverage.none.fl_str_mv |
Clifton, NJ |
dc.publisher.none.fl_str_mv |
Humana Press |
publisher.none.fl_str_mv |
Humana Press |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
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