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

Lookup NU author(s): Dr Sharon Cookson, Santosh Murali, Dr John Perry, Dr Clare Lanyon, Professor Anthony De Soyza, Dr Stephen Todryk

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 The Author(s). 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 FEV1% (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.


Publication metadata

Author(s): Jaat FG, Hasan SF, Perry A, Cookson S, Murali S, Perry JD, Lanyon CV, De Soyza A, Todryk SM

Publication type: Article

Publication status: Published

Journal: Respiratory Research

Year: 2018

Volume: 19

Online publication date: 30/05/2018

Acceptance date: 14/05/2018

Date deposited: 20/06/2018

ISSN (print): 1465-9921

ISSN (electronic): 1465-993X

Publisher: BioMed Central Ltd

URL: https://doi.org/10.1186/s12931-018-0811-2

DOI: 10.1186/s12931-018-0811-2


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