Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid

Abstract Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same l...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Gustavo C. Nascimento-Carvalho, Eduardo C. Nascimento-Carvalho, Clara L. Ramos, Ana-Luisa Vilas-Boas, Otávio A. Moreno-Carvalho, Caian L. Vinhaes, Beatriz Barreto-Duarte, Artur T. L. Queiroz, Bruno B. Andrade, Cristiana M. Nascimento-Carvalho
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/6edef74aae5a4a818c4383510cc58623
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:6edef74aae5a4a818c4383510cc58623
record_format dspace
spelling oai:doaj.org-article:6edef74aae5a4a818c4383510cc586232021-12-02T17:32:58ZZika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid10.1038/s41598-021-87895-42045-2322https://doaj.org/article/6edef74aae5a4a818c4383510cc586232021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87895-4https://doaj.org/toc/2045-2322Abstract Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015–2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017–2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P < 0.0001). Between controls and those non-microcephalic exposed to ZIKV, IL-1β, IL-3, IL-4, IL-7 and EOTAXIN were the top CSF markers. By comparing the microcephalic cases with controls, the top discriminant scores were for IL-1β, IL-3, EOTAXIN and IL-12p70. The degree of inflammatory imbalance may be associated with microcephaly in CZI and it may aid additional investigations in experimental pre-clinical models testing immune modulators in preventing extensive damage of the Central Nervous System.Gustavo C. Nascimento-CarvalhoEduardo C. Nascimento-CarvalhoClara L. RamosAna-Luisa Vilas-BoasOtávio A. Moreno-CarvalhoCaian L. VinhaesBeatriz Barreto-DuarteArtur T. L. QueirozBruno B. AndradeCristiana M. Nascimento-CarvalhoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Gustavo C. Nascimento-Carvalho
Eduardo C. Nascimento-Carvalho
Clara L. Ramos
Ana-Luisa Vilas-Boas
Otávio A. Moreno-Carvalho
Caian L. Vinhaes
Beatriz Barreto-Duarte
Artur T. L. Queiroz
Bruno B. Andrade
Cristiana M. Nascimento-Carvalho
Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid
description Abstract Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015–2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017–2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P < 0.0001). Between controls and those non-microcephalic exposed to ZIKV, IL-1β, IL-3, IL-4, IL-7 and EOTAXIN were the top CSF markers. By comparing the microcephalic cases with controls, the top discriminant scores were for IL-1β, IL-3, EOTAXIN and IL-12p70. The degree of inflammatory imbalance may be associated with microcephaly in CZI and it may aid additional investigations in experimental pre-clinical models testing immune modulators in preventing extensive damage of the Central Nervous System.
format article
author Gustavo C. Nascimento-Carvalho
Eduardo C. Nascimento-Carvalho
Clara L. Ramos
Ana-Luisa Vilas-Boas
Otávio A. Moreno-Carvalho
Caian L. Vinhaes
Beatriz Barreto-Duarte
Artur T. L. Queiroz
Bruno B. Andrade
Cristiana M. Nascimento-Carvalho
author_facet Gustavo C. Nascimento-Carvalho
Eduardo C. Nascimento-Carvalho
Clara L. Ramos
Ana-Luisa Vilas-Boas
Otávio A. Moreno-Carvalho
Caian L. Vinhaes
Beatriz Barreto-Duarte
Artur T. L. Queiroz
Bruno B. Andrade
Cristiana M. Nascimento-Carvalho
author_sort Gustavo C. Nascimento-Carvalho
title Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid
title_short Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid
title_full Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid
title_fullStr Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid
title_full_unstemmed Zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid
title_sort zika-exposed microcephalic neonates exhibit higher degree of inflammatory imbalance in cerebrospinal fluid
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/6edef74aae5a4a818c4383510cc58623
work_keys_str_mv AT gustavocnascimentocarvalho zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT eduardocnascimentocarvalho zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT claralramos zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT analuisavilasboas zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT otavioamorenocarvalho zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT caianlvinhaes zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT beatrizbarretoduarte zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT arturtlqueiroz zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT brunobandrade zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
AT cristianamnascimentocarvalho zikaexposedmicrocephalicneonatesexhibithigherdegreeofinflammatoryimbalanceincerebrospinalfluid
_version_ 1718380126141415424