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Maternal BCG scar is associated with increased infant proinflammatory immune responses

INTRODUCTION: Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-...

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Autores principales: Mawa, Patrice Akusa, Webb, Emily L., Filali-Mouhim, Abdelali, Nkurunungi, Gyaviira, Sekaly, Rafick-Pierre, Lule, Swaib Abubaker, Prentice, Sarah, Nash, Stephen, Dockrell, Hazel M., Elliott, Alison M., Cose, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357573/
https://www.ncbi.nlm.nih.gov/pubmed/27914741
http://dx.doi.org/10.1016/j.vaccine.2016.11.079
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author Mawa, Patrice Akusa
Webb, Emily L.
Filali-Mouhim, Abdelali
Nkurunungi, Gyaviira
Sekaly, Rafick-Pierre
Lule, Swaib Abubaker
Prentice, Sarah
Nash, Stephen
Dockrell, Hazel M.
Elliott, Alison M.
Cose, Stephen
author_facet Mawa, Patrice Akusa
Webb, Emily L.
Filali-Mouhim, Abdelali
Nkurunungi, Gyaviira
Sekaly, Rafick-Pierre
Lule, Swaib Abubaker
Prentice, Sarah
Nash, Stephen
Dockrell, Hazel M.
Elliott, Alison M.
Cose, Stephen
author_sort Mawa, Patrice Akusa
collection PubMed
description INTRODUCTION: Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants. MATERIAL AND METHODS: Maternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24 h and cytokines and chemokines in supernatants were measured using the Luminex® assay. The associations between maternal latent Mycobacterium tuberculosis infection (LTBI), maternal BCG scar (adjusted for each other’s effect) and infant responses were examined using linear regression. Principal Component Analysis (PCA) was used to assess patterns of cytokine and chemokine responses. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n = 42) and six (n = 51) weeks after BCG immunisation using microarray. RESULTS: Maternal LTBI was positively associated with infant IP-10 responses with an adjusted geometric mean ratio (aGMR) [95% confidence interval (CI)] of 5.10 [1.21, 21.48]. Maternal BCG scar showed strong and consistent associations with IFN-γ (aGMR 2.69 [1.15, 6.17]), IL-12p70 (1.95 [1.10, 3.55]), IL-10 (1.82 [1.07, 3.09]), VEGF (3.55 [1.07, 11.48]) and IP-10 (6.76 [1.17, 38.02]). Further assessment of the associations using PCA showed no differences for maternal LTBI, but maternal BCG scar was associated with higher scores for principal component (PC) 1 (median level of scores: 1.44 in scar-positive versus −0.94 in scar-negative, p = 0.020) in the infants. PC1 represented a controlled proinflammatory response. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation. CONCLUSIONS: Maternal BCG scar had a stronger association with infant responses than maternal LTBI, with an increased proinflammatory immune profile.
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spelling pubmed-53575732017-03-19 Maternal BCG scar is associated with increased infant proinflammatory immune responses Mawa, Patrice Akusa Webb, Emily L. Filali-Mouhim, Abdelali Nkurunungi, Gyaviira Sekaly, Rafick-Pierre Lule, Swaib Abubaker Prentice, Sarah Nash, Stephen Dockrell, Hazel M. Elliott, Alison M. Cose, Stephen Vaccine Article INTRODUCTION: Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of innate responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on BCG vaccine-induced responses in Ugandan infants. MATERIAL AND METHODS: Maternal and cord blood samples from 29 mother-infant pairs were stimulated with innate stimuli for 24 h and cytokines and chemokines in supernatants were measured using the Luminex® assay. The associations between maternal latent Mycobacterium tuberculosis infection (LTBI), maternal BCG scar (adjusted for each other’s effect) and infant responses were examined using linear regression. Principal Component Analysis (PCA) was used to assess patterns of cytokine and chemokine responses. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n = 42) and six (n = 51) weeks after BCG immunisation using microarray. RESULTS: Maternal LTBI was positively associated with infant IP-10 responses with an adjusted geometric mean ratio (aGMR) [95% confidence interval (CI)] of 5.10 [1.21, 21.48]. Maternal BCG scar showed strong and consistent associations with IFN-γ (aGMR 2.69 [1.15, 6.17]), IL-12p70 (1.95 [1.10, 3.55]), IL-10 (1.82 [1.07, 3.09]), VEGF (3.55 [1.07, 11.48]) and IP-10 (6.76 [1.17, 38.02]). Further assessment of the associations using PCA showed no differences for maternal LTBI, but maternal BCG scar was associated with higher scores for principal component (PC) 1 (median level of scores: 1.44 in scar-positive versus −0.94 in scar-negative, p = 0.020) in the infants. PC1 represented a controlled proinflammatory response. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation. CONCLUSIONS: Maternal BCG scar had a stronger association with infant responses than maternal LTBI, with an increased proinflammatory immune profile. Elsevier Science 2017-01-05 /pmc/articles/PMC5357573/ /pubmed/27914741 http://dx.doi.org/10.1016/j.vaccine.2016.11.079 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mawa, Patrice Akusa
Webb, Emily L.
Filali-Mouhim, Abdelali
Nkurunungi, Gyaviira
Sekaly, Rafick-Pierre
Lule, Swaib Abubaker
Prentice, Sarah
Nash, Stephen
Dockrell, Hazel M.
Elliott, Alison M.
Cose, Stephen
Maternal BCG scar is associated with increased infant proinflammatory immune responses
title Maternal BCG scar is associated with increased infant proinflammatory immune responses
title_full Maternal BCG scar is associated with increased infant proinflammatory immune responses
title_fullStr Maternal BCG scar is associated with increased infant proinflammatory immune responses
title_full_unstemmed Maternal BCG scar is associated with increased infant proinflammatory immune responses
title_short Maternal BCG scar is associated with increased infant proinflammatory immune responses
title_sort maternal bcg scar is associated with increased infant proinflammatory immune responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357573/
https://www.ncbi.nlm.nih.gov/pubmed/27914741
http://dx.doi.org/10.1016/j.vaccine.2016.11.079
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