Relationships between mucosal antibodies, non-typeable haemophilus influenzae (NTHi) infection and airway inflammation in COPD

Karl J. Staples, Stephen Taylor, Steve Thomas, Stephanie Leung, Karen Cox, Thierry G. Pascal, Kristoffer Ostridge, Lindsay Welch, Andrew C Tuck, Stuart C Clarke, Andrew Gorringe, Thomas Wilkinson

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalPLoS One
DOIs
Publication statusPublished - 29 Nov 2016

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Haemophilus Infections
Haemophilus influenzae
Chronic Obstructive Pulmonary Disease
Immunoglobulin G
inflammation
Inflammation
antibodies
Antibodies
infection
Immunoglobulin A
Immunoglobulin M
Bronchoalveolar Lavage
Pathogens
Interleukin-1
lungs
bronchoscopy
Health
mucosal immunity
Mucosal Immunity
Lung

Cite this

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 ; Wilkinson, Thomas. / Relationships between mucosal antibodies, non-typeable haemophilus influenzae (NTHi) infection and airway inflammation in COPD. In: PLoS One. 2016 ; pp. 1-17.
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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.",
author = "Staples, {Karl J.} and Stephen Taylor and Steve Thomas and Stephanie Leung and Karen Cox and Pascal, {Thierry G.} and Kristoffer Ostridge and Lindsay Welch and Tuck, {Andrew C} and Clarke, {Stuart C} and Andrew Gorringe and Thomas Wilkinson",
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Staples, KJ, Taylor, S, Thomas, S, Leung, S, Cox, K, Pascal, TG, Ostridge, K, Welch, L, Tuck, AC, Clarke, SC, Gorringe, A & Wilkinson, T 2016, 'Relationships between mucosal antibodies, non-typeable haemophilus influenzae (NTHi) infection and airway inflammation in COPD' PLoS One, pp. 1-17. https://doi.org/10.1371/journal.pone.0167250

Relationships between mucosal antibodies, non-typeable haemophilus influenzae (NTHi) infection and airway inflammation in COPD. / 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; Wilkinson, Thomas.

In: PLoS One, 29.11.2016, p. 1-17.

Research output: Contribution to journalArticle

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T1 - Relationships between mucosal antibodies, non-typeable haemophilus influenzae (NTHi) infection and airway inflammation in COPD

AU - Staples, Karl J.

AU - Taylor, Stephen

AU - Thomas, Steve

AU - Leung, Stephanie

AU - Cox, Karen

AU - Pascal, Thierry G.

AU - Ostridge, Kristoffer

AU - Welch, Lindsay

AU - Tuck, Andrew C

AU - Clarke, Stuart C

AU - Gorringe, Andrew

AU - Wilkinson, Thomas

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N2 - 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.

AB - 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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DO - 10.1371/journal.pone.0167250

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