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Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease

BACKGROUND: As a way to determine markers of infection or disease informing disease management, and to reveal disease-associated immune mechanisms, this study sought to measure antibody and T cell responses against key lung pathogens and to relate these to patients’ microbial colonization status, ex...

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Autores principales: Jaat, Fathia G., Hasan, Sajidah F., Perry, Audrey, Cookson, Sharon, Murali, Santosh, Perry, John D., Lanyon, Clare V., De Soyza, Anthony, Todryk, Stephen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977760/
https://www.ncbi.nlm.nih.gov/pubmed/29848315
http://dx.doi.org/10.1186/s12931-018-0811-2
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author Jaat, Fathia G.
Hasan, Sajidah F.
Perry, Audrey
Cookson, Sharon
Murali, Santosh
Perry, John D.
Lanyon, Clare V.
De Soyza, Anthony
Todryk, Stephen M.
author_facet Jaat, Fathia G.
Hasan, Sajidah F.
Perry, Audrey
Cookson, Sharon
Murali, Santosh
Perry, John D.
Lanyon, Clare V.
De Soyza, Anthony
Todryk, Stephen M.
author_sort Jaat, Fathia G.
collection PubMed
description BACKGROUND: As a way to determine markers of infection or disease informing disease management, and to reveal disease-associated immune mechanisms, this study sought to measure antibody and T cell responses against key lung pathogens and to relate these to patients’ microbial colonization status, exacerbation history and lung function, in Bronchiectasis (BR) and Chronic Obstructive Pulmonary Disease (COPD). METHODS: One hundred nineteen patients with stable BR, 58 with COPD and 28 healthy volunteers were recruited and spirometry was performed. Bacterial lysates were used to measure specific antibody responses by ELISA and T cells by ELIspot. Cytokine secretion by lysate-stimulated T cells was measured by multiplex cytokine assay whilst activation phenotype was measured by flow cytometry. RESULTS: Typical colonization profiles were observed in BR and COPD, dominated by P.aeruginosa, H.influenzae, S.pneumoniae and M.catarrhalis. Colonization frequency was greater in BR, showing association with increased antibody responses against P.aeruginosa compared to COPD and HV, and with sensitivity of 73% and specificity of 95%. Interferon-gamma T cell responses against P.aeruginosa and S.pneumoniae were reduced in BR and COPD, whilst reactive T cells in BR had similar markers of homing and senescence compared to healthy volunteers. Exacerbation frequency in BR was associated with increased antibodies against P. aeruginosa, M.catarrhalis and S.maltophilia. T cell responses against H.influenzae showed positive correlation with FEV(1)% (r = 0.201, p = 0.033) and negative correlation with Bronchiectasis Severity Index (r = − 0.287, p = 0.0035). CONCLUSION: Our findings suggest a difference in antibody and T cell immunity in BR, with antibody being a marker of exposure and disease in BR for P.aeruginosa, M.catarrhalis and H.influenzae, and T cells a marker of reduced disease for H.influenzae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0811-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-59777602018-06-06 Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease Jaat, Fathia G. Hasan, Sajidah F. Perry, Audrey Cookson, Sharon Murali, Santosh Perry, John D. Lanyon, Clare V. De Soyza, Anthony Todryk, Stephen M. Respir Res Research BACKGROUND: As a way to determine markers of infection or disease informing disease management, and to reveal disease-associated immune mechanisms, this study sought to measure antibody and T cell responses against key lung pathogens and to relate these to patients’ microbial colonization status, exacerbation history and lung function, in Bronchiectasis (BR) and Chronic Obstructive Pulmonary Disease (COPD). METHODS: One hundred nineteen patients with stable BR, 58 with COPD and 28 healthy volunteers were recruited and spirometry was performed. Bacterial lysates were used to measure specific antibody responses by ELISA and T cells by ELIspot. Cytokine secretion by lysate-stimulated T cells was measured by multiplex cytokine assay whilst activation phenotype was measured by flow cytometry. RESULTS: Typical colonization profiles were observed in BR and COPD, dominated by P.aeruginosa, H.influenzae, S.pneumoniae and M.catarrhalis. Colonization frequency was greater in BR, showing association with increased antibody responses against P.aeruginosa compared to COPD and HV, and with sensitivity of 73% and specificity of 95%. Interferon-gamma T cell responses against P.aeruginosa and S.pneumoniae were reduced in BR and COPD, whilst reactive T cells in BR had similar markers of homing and senescence compared to healthy volunteers. Exacerbation frequency in BR was associated with increased antibodies against P. aeruginosa, M.catarrhalis and S.maltophilia. T cell responses against H.influenzae showed positive correlation with FEV(1)% (r = 0.201, p = 0.033) and negative correlation with Bronchiectasis Severity Index (r = − 0.287, p = 0.0035). CONCLUSION: Our findings suggest a difference in antibody and T cell immunity in BR, with antibody being a marker of exposure and disease in BR for P.aeruginosa, M.catarrhalis and H.influenzae, and T cells a marker of reduced disease for H.influenzae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0811-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-05-30 2018 /pmc/articles/PMC5977760/ /pubmed/29848315 http://dx.doi.org/10.1186/s12931-018-0811-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Jaat, Fathia G.
Hasan, Sajidah F.
Perry, Audrey
Cookson, Sharon
Murali, Santosh
Perry, John D.
Lanyon, Clare V.
De Soyza, Anthony
Todryk, Stephen M.
Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease
title Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease
title_full Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease
title_fullStr Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease
title_full_unstemmed Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease
title_short Anti-bacterial antibody and T cell responses in bronchiectasis are differentially associated with lung colonization and disease
title_sort anti-bacterial antibody and t cell responses in bronchiectasis are differentially associated with lung colonization and disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977760/
https://www.ncbi.nlm.nih.gov/pubmed/29848315
http://dx.doi.org/10.1186/s12931-018-0811-2
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