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High levels of anti-Leishmania IgG3 and low CD4(+) T cells count were associated with relapses in visceral leishmaniasis

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, so...

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Autores principales: Kuschnir, Renata Caetano, Pereira, Leonardo Soares, Dutra, Maria Rita Teixeira, de Paula, Ludmila, Silva-Freitas, Maria Luciana, Corrêa-Castro, Gabriela, da Costa Cruz Silva, Simone, Cota, Glaucia, Santos-Oliveira, Joanna Reis, Da-Cruz, Alda Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056614/
https://www.ncbi.nlm.nih.gov/pubmed/33874901
http://dx.doi.org/10.1186/s12879-021-06051-5
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author Kuschnir, Renata Caetano
Pereira, Leonardo Soares
Dutra, Maria Rita Teixeira
de Paula, Ludmila
Silva-Freitas, Maria Luciana
Corrêa-Castro, Gabriela
da Costa Cruz Silva, Simone
Cota, Glaucia
Santos-Oliveira, Joanna Reis
Da-Cruz, Alda Maria
author_facet Kuschnir, Renata Caetano
Pereira, Leonardo Soares
Dutra, Maria Rita Teixeira
de Paula, Ludmila
Silva-Freitas, Maria Luciana
Corrêa-Castro, Gabriela
da Costa Cruz Silva, Simone
Cota, Glaucia
Santos-Oliveira, Joanna Reis
Da-Cruz, Alda Maria
author_sort Kuschnir, Renata Caetano
collection PubMed
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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06051-5.
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spelling pubmed-80566142021-04-20 High levels of anti-Leishmania IgG3 and low CD4(+) T cells count were associated with relapses in visceral leishmaniasis Kuschnir, Renata Caetano Pereira, Leonardo Soares Dutra, Maria Rita Teixeira de Paula, Ludmila Silva-Freitas, Maria Luciana Corrêa-Castro, Gabriela da Costa Cruz Silva, Simone Cota, Glaucia Santos-Oliveira, Joanna Reis Da-Cruz, Alda Maria BMC Infect Dis Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06051-5. BioMed Central 2021-04-20 /pmc/articles/PMC8056614/ /pubmed/33874901 http://dx.doi.org/10.1186/s12879-021-06051-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kuschnir, Renata Caetano
Pereira, Leonardo Soares
Dutra, Maria Rita Teixeira
de Paula, Ludmila
Silva-Freitas, Maria Luciana
Corrêa-Castro, Gabriela
da Costa Cruz Silva, Simone
Cota, Glaucia
Santos-Oliveira, Joanna Reis
Da-Cruz, Alda Maria
High levels of anti-Leishmania IgG3 and low CD4(+) T cells count were associated with relapses in visceral leishmaniasis
title 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_short 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056614/
https://www.ncbi.nlm.nih.gov/pubmed/33874901
http://dx.doi.org/10.1186/s12879-021-06051-5
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