High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1186/s12879-021-06051-5 http://hdl.handle.net/1843/55281 https://orcid.org/0000-0002-5426-0655 https://orcid.org/0000-0002-3352-616X https://orcid.org/0000-0002-9899-8547 https://orcid.org/0000-0003-0538-7403 https://orcid.org/0000-0003-3155-6717 https://orcid.org/0000-0001-7455-2447 |
Resumo: | Background: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4+ T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1β), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4–5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL. Methods: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4+ and CD8+ T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls. Results: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4+ T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4+ T counts in the R-VL group (r = − 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity. Conclusions: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses. |
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2023-06-23T19:29:59Z2023-06-23T19:29:59Z2021-04-2021https://doi.org/10.1186/s12879-021-06051-51471-2334http://hdl.handle.net/1843/55281https://orcid.org/0000-0002-5426-0655https://orcid.org/0000-0002-3352-616Xhttps://orcid.org/0000-0002-9899-8547https://orcid.org/0000-0003-0538-7403https://orcid.org/0000-0003-3155-6717https://orcid.org/0000-0001-7455-2447Background: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4+ T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1β), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4–5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL. Methods: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4+ and CD8+ T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls. Results: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4+ T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4+ T counts in the R-VL group (r = − 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity. Conclusions: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses.Introdução: A leishmaniose visceral (LV) é grave e potencialmente fatal. O Brasil é um dos países com maior endemicidade da doença no mundo. A redução de linfócitos T CD4+, ativação de células B e altos níveis de citocinas inflamatórias (IL-6/IL-8/TNF/IL-1β), LPS plasmático, CD14 solúvel, anti-Leishmania IgG3 e baixos níveis de leptina estão envolvidos no imunopatogênese da LV, mais associada à LV grave. Apesar das recaídas ocorrerem em cerca de 4 a 5% dos pacientes com LV não associada à infecção pelo HIV, os fatores subjacentes às recaídas são pouco conhecidos. Nosso objetivo foi identificar parâmetros clínicos, laboratoriais e imunológicos que possam estar associados a recidivas na LV. Métodos: Quinze pacientes com LV recrutados no Hospital Eduardo de Menezes (BH-MG) foram agrupados em recidivantes (R-VL, n = 5) e não recidivantes (NR-VL, n = 10) e avaliados durante a doença ativa, imediatamente após tratamento (pós-tratamento) e 6 meses pós-tratamento (6mpt). Dados clínicos e laboratoriais obtidos de prontuários médicos foram correlacionados com contagens de células T CD4+ e CD8+ e níveis plasmáticos de anti-Leishmania Igs e IL-6 e comparados com esses parâmetros de dez controles saudáveis. Resultados: Durante a fase ativa da LV, apesar da semelhança nos sintomas clínicos, as taxas de trombocitopenia, transaminases elevadas (AST e ALT) e hiperbilirrubinemia foram maiores no grupo NR-VL em comparação com R-VL (p < 0,05), um perfil revertido durante a fase pós-tratamento. Todos os pacientes apresentaram baixa contagem de CD4+ T na fase ativa, porém, os pacientes NR-VL tiveram maior ganho deste tipo celular do que R-VL no pós-tratamento (p < 0,05). Houve redução significativa dos níveis de IgG3 durante o seguimento no grupo NR-VL em relação ao R-VL, principalmente no 6mpt (p < 0,05). Além disso, os níveis de IgG3 foram negativamente correlacionados com as contagens de CD4+ T no grupo R-VL (r = − 0,52). Níveis elevados de IL-6 foram observados na LV ativa e correlacionados com marcadores clínicos de gravidade. Conclusões: Durante a fase ativa da LV, os pacientes NR-VL apresentaram anormalidades laboratoriais mais graves em relação aos R-VL, provavelmente porque estes últimos já haviam recebido tratamento prévio. Por outro lado, R-VL apresentou maior comprometimento da reconstituição imune e alto grau de ativação de linfócitos B, o que deve ser um fator que favoreceu as recidivas.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de JaneiroOutra AgênciaengUniversidade Federal de Minas GeraisUFMGBrasilHCL - HOSPITAL DAS CLINICASBMC Infectious DiseasesLeishmaniose visceralRecidivaContinuidade da assistência ao pacienteImunidadeVisceral leishmaniasisRelapsesClinical follow-upImmune responseHigh levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasisAltos níveis de IgG3 anti-leishmania e baixa contagem de células T CD4+ foram associados a recidivas na leishmaniose visceralinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06051-5Renata Caetano KuschnirLeonardo Soares PereiraMaria Rita Teixeira DutraLudmila de PaulaMaria Luciana Silva de FreitasGabriela Corrêa e CastroSimone da Costa Cruz SilvaGlaucia Fernandes CotaJoanna Reis Santos de OliveiraAlda Maria Da Cruzapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/55281/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALHigh levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis.pdfHigh levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis.pdfapplication/pdf1299826https://repositorio.ufmg.br/bitstream/1843/55281/2/High%20levels%20of%20anti-leishmania%20IgG3%20and%20low%20CD4%2b%20T%20cells%20count%20were%20associated%20with%20relapses%20in%20visceral%20leishmaniasis.pdfe9e96554a724ac5cc8a0f48a05fadccdMD521843/552812023-06-23 16:29:59.891oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-06-23T19:29:59Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis |
dc.title.alternative.pt_BR.fl_str_mv |
Altos níveis de IgG3 anti-leishmania e baixa contagem de células T CD4+ foram associados a recidivas na leishmaniose visceral |
title |
High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis |
spellingShingle |
High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis Renata Caetano Kuschnir Visceral leishmaniasis Relapses Clinical follow-up Immune response Leishmaniose visceral Recidiva Continuidade da assistência ao paciente Imunidade |
title_short |
High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis |
title_full |
High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis |
title_fullStr |
High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis |
title_full_unstemmed |
High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis |
title_sort |
High levels of anti-leishmania IgG3 and low CD4+ T cells count were associated with relapses in visceral leishmaniasis |
author |
Renata Caetano Kuschnir |
author_facet |
Renata Caetano Kuschnir Leonardo Soares Pereira Maria Rita Teixeira Dutra Ludmila de Paula Maria Luciana Silva de Freitas Gabriela Corrêa e Castro Simone da Costa Cruz Silva Glaucia Fernandes Cota Joanna Reis Santos de Oliveira Alda Maria Da Cruz |
author_role |
author |
author2 |
Leonardo Soares Pereira Maria Rita Teixeira Dutra Ludmila de Paula Maria Luciana Silva de Freitas Gabriela Corrêa e Castro Simone da Costa Cruz Silva Glaucia Fernandes Cota Joanna Reis Santos de Oliveira Alda Maria Da Cruz |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Renata Caetano Kuschnir Leonardo Soares Pereira Maria Rita Teixeira Dutra Ludmila de Paula Maria Luciana Silva de Freitas Gabriela Corrêa e Castro Simone da Costa Cruz Silva Glaucia Fernandes Cota Joanna Reis Santos de Oliveira Alda Maria Da Cruz |
dc.subject.por.fl_str_mv |
Visceral leishmaniasis Relapses Clinical follow-up Immune response |
topic |
Visceral leishmaniasis Relapses Clinical follow-up Immune response Leishmaniose visceral Recidiva Continuidade da assistência ao paciente Imunidade |
dc.subject.other.pt_BR.fl_str_mv |
Leishmaniose visceral Recidiva Continuidade da assistência ao paciente Imunidade |
description |
Background: Visceral leishmaniasis (VL) is severe and potentially fatal. Brazil is one of the countries with the greatest endemicity for the disease in the world. The reduction of CD4+ T lymphocytes, B cells activation and high levels of inflammatory cytokines (IL-6/IL-8/TNF/IL-1β), plasma LPS, soluble CD14, anti-Leishmania IgG3 and low leptin levels are involved in the immunopathogenesis of VL, most associated with severe VL. Despite relapses occurring in about 4–5% of patients with VL not associated with HIV infection, the factors underlying relapses are little known. Our aim was to identify clinical, laboratory and immunological parameters that may be associated with recurrences in VL. Methods: Fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were grouped into relapsing (R-VL, n = 5) and non-relapsing (NR-VL, n = 10) and evaluated during active disease, immediately after treatment (post-treatment) and 6 months post-treatment (6mpt). Clinical and laboratory data obtained from medical records were correlated with CD4+ and CD8+ T cell counts and anti-Leishmania Igs and IL-6 plasma levels and compared to those parameters of ten healthy controls. Results: During the active phase of VL, despite similarity in the clinical symptoms, the rates of thrombocytopenia, elevated transaminases (AST and ALT) and hyperbilirubinemia were higher in the NR-VL group compared to R-VL (p < 0.05), a profile reversed during the post-treatment phase. All patients had low CD4+ T counts in active phase, however, NR-VL patients had a higher gain of this cell type than R-VL in the post-treatment (p < 0.05). There was a significant reduction in IgG3 levels during the follow-up in the NR-VL group compared to the R-VL, especially at 6mpt (p < 0.05). In addition, IgG3 levels were negatively correlated with CD4+ T counts in the R-VL group (r = − 0.52). Elevated levels of IL-6 were observed in active VL and correlated with clinical markers of severity. Conclusions: During active phase of VL, the NR-VL patients presented more severe laboratorial abnormalities compared to R-VL, probably because the latter had already received previous treatment. On the other hand, R-VL exhibited greater impairment of immune reconstitution and a high degree of B lymphocyte activation, which must be a factor that favored relapses. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-04-20 |
dc.date.accessioned.fl_str_mv |
2023-06-23T19:29:59Z |
dc.date.available.fl_str_mv |
2023-06-23T19:29:59Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/55281 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1186/s12879-021-06051-5 |
dc.identifier.issn.pt_BR.fl_str_mv |
1471-2334 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-5426-0655 https://orcid.org/0000-0002-3352-616X https://orcid.org/0000-0002-9899-8547 https://orcid.org/0000-0003-0538-7403 https://orcid.org/0000-0003-3155-6717 https://orcid.org/0000-0001-7455-2447 |
url |
https://doi.org/10.1186/s12879-021-06051-5 http://hdl.handle.net/1843/55281 https://orcid.org/0000-0002-5426-0655 https://orcid.org/0000-0002-3352-616X https://orcid.org/0000-0002-9899-8547 https://orcid.org/0000-0003-0538-7403 https://orcid.org/0000-0003-3155-6717 https://orcid.org/0000-0001-7455-2447 |
identifier_str_mv |
1471-2334 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
BMC Infectious Diseases |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
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HCL - HOSPITAL DAS CLINICAS |
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Universidade Federal de Minas Gerais |
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