Relationships between mucosal antibodies, non-typeable haemophilus influenzae (NTHi) infection and airway inflammation in COPD
Relationships between mucosal antibodies, non-typeable haemophilus influenzae (NTHi) infection and airway inflammation in COPD
Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD. Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls.
BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls. NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve - 29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation. When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p=0.0068) and NTHi-specific IgG1 (p=0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM. We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway. Furthermore, the NTHi+ve patients had significantly greater levels of IL-1? (p=0.0003), in BAL than NTHi-ve COPD patients.
This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients. This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi.
1-17
Staples, Karl J.
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Taylor, Stephen
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Thomas, Steve
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Leung, Stephanie
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Cox, Karen
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Pascal, Thierry G.
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Ostridge, Kristoffer
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Welch, Lindsay
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Tuck, Andrew C
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Clarke, Stuart C
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Gorringe, Andrew
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Wilkinson, Thomas
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29 November 2016
Staples, Karl J.
e0e9d80f-0aed-435f-bd75-0c8818491fee
Taylor, Stephen
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Thomas, Steve
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Leung, Stephanie
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Cox, Karen
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Pascal, Thierry G.
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Ostridge, Kristoffer
d2271bae-b078-4390-8919-8f8c0e20542c
Welch, Lindsay
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Tuck, Andrew C
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Clarke, Stuart C
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Gorringe, Andrew
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Wilkinson, Thomas
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Staples, Karl J., Taylor, Stephen, Thomas, Steve, Leung, Stephanie, Cox, Karen, Pascal, Thierry G., Ostridge, Kristoffer, Welch, Lindsay, Tuck, Andrew C, Clarke, Stuart C, Gorringe, Andrew and Wilkinson, Thomas
(2016)
Relationships between mucosal antibodies, non-typeable haemophilus influenzae (NTHi) infection and airway inflammation in COPD.
PLoS ONE, .
(doi:10.1371/journal.pone.0167250).
(PMID:27898728)
Abstract
Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation. Why some patients are susceptible to colonisation is not understood. We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity. The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD. Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls.
BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls. NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve - 29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation. When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p=0.0068) and NTHi-specific IgG1 (p=0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM. We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway. Furthermore, the NTHi+ve patients had significantly greater levels of IL-1? (p=0.0003), in BAL than NTHi-ve COPD patients.
This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients. This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi.
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Accepted/In Press date: 10 November 2016
e-pub ahead of print date: 29 November 2016
Published date: 29 November 2016
Organisations:
NIHR Southampton Respiratory Biomedical Research Unit, Clinical & Experimental Sciences
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Local EPrints ID: 403415
URI: http://eprints.soton.ac.uk/id/eprint/403415
ISSN: 1932-6203
PURE UUID: 70bde7e0-8446-46a0-8999-05a608ab4b2e
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Date deposited: 30 Nov 2016 12:34
Last modified: 16 Mar 2024 03:52
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Author:
Stephen Taylor
Author:
Steve Thomas
Author:
Stephanie Leung
Author:
Karen Cox
Author:
Thierry G. Pascal
Author:
Kristoffer Ostridge
Author:
Andrew C Tuck
Author:
Andrew Gorringe
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