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Immunological profiling of key inflammatory drivers of nasal polyp formation and growth in chronic rhinosinusitis

Immunological profiling of key inflammatory drivers of nasal polyp formation and growth in chronic rhinosinusitis
Immunological profiling of key inflammatory drivers of nasal polyp formation and growth in chronic rhinosinusitis
Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the upper airways, often associated with the formation of nasal polyps (CRSwNP). It is well established that macroscopically normal (non-polypoidal) sinonasal mucosa in CRSwNP patients can undergo polypoidal change over time, turning into frank polyps. However, little is known about what drives this process. This study aimed to investigate potential drivers of nasal polyp formation or growth through comparison of the immunological profiles of nasal polyps with contiguous non-polypoidal sinonasal mucosa, from the same patients.

Methods: The immune profiles of three types of tissue were compared; nasal polyps and adjacent non-polypoidal sinonasal mucosa from 10 CRSwNP patients, and sinonasal mucosa from 10 control patients undergoing trans-sphenoidal pituitary surgery. Nasal polyp and control samples were also stimulated with Staphylococcus aureus enterotoxin B (SEB) using a nasal explant model, prior to cytokine analysis. Real time quantitative polymerase chain reaction (IL-5, T-bet, IL-17A, FoxP3, TLR-4, IL-8, IL-1β and IL-6) and Luminex (IFNγ, IL-5 and IL-17A) were used to quantify pro-inflammatory responses.

Results: Nasal polyps and contiguous non-polypoidal sinonasal mucosa from CRSwNP patients displayed a very similar pro-inflammatory profile. When stimulated with SEB, nasal polyps displayed a Th2/Th17 mediated response when compared to controls.

Conclusions: In CRSwNP, nasal polyps and non-polypoidal sinonasal mucosa from the same patient displayed a similar pro-inflammatory profile skewed towards the Th2/Th17 pathway in nasal polyps following SEB stimulation, with evidence of disordered bacterial clearance. These factors may contribute to enhanced survival of bacteria and development of a chronic inflammatory milieu, potentially driving new polyp formation and recurrence following surgical removal.
chronic rhinosinusitis, immunology, Inflammation, Nasal polyps
0300-0729
336-342
Biggs, Timothy, Charles
887596b4-f2ad-4067-8f01-5f2cfe1ae394
Hayes, Stephen
7c6543a2-17a4-4629-91bb-bb64965df66a
Harries, Philip G.
df33be64-b580-4fdf-ac4d-4c842b55d753
Allan, Raymond
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1
Walls, Andrew
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Salib, Rami
d6fde1c1-5b5e-43f7-ae1c-42cce6a0c9fc
Biggs, Timothy, Charles
887596b4-f2ad-4067-8f01-5f2cfe1ae394
Hayes, Stephen
7c6543a2-17a4-4629-91bb-bb64965df66a
Harries, Philip G.
df33be64-b580-4fdf-ac4d-4c842b55d753
Allan, Raymond
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1
Walls, Andrew
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Salib, Rami
d6fde1c1-5b5e-43f7-ae1c-42cce6a0c9fc

Biggs, Timothy, Charles, Hayes, Stephen, Harries, Philip G., Allan, Raymond, Walls, Andrew, Pender, Sylvia and Salib, Rami (2019) Immunological profiling of key inflammatory drivers of nasal polyp formation and growth in chronic rhinosinusitis. Rhinology, 57 (5), 336-342. (doi:10.4193/Rhin19.167).

Record type: Article

Abstract

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the upper airways, often associated with the formation of nasal polyps (CRSwNP). It is well established that macroscopically normal (non-polypoidal) sinonasal mucosa in CRSwNP patients can undergo polypoidal change over time, turning into frank polyps. However, little is known about what drives this process. This study aimed to investigate potential drivers of nasal polyp formation or growth through comparison of the immunological profiles of nasal polyps with contiguous non-polypoidal sinonasal mucosa, from the same patients.

Methods: The immune profiles of three types of tissue were compared; nasal polyps and adjacent non-polypoidal sinonasal mucosa from 10 CRSwNP patients, and sinonasal mucosa from 10 control patients undergoing trans-sphenoidal pituitary surgery. Nasal polyp and control samples were also stimulated with Staphylococcus aureus enterotoxin B (SEB) using a nasal explant model, prior to cytokine analysis. Real time quantitative polymerase chain reaction (IL-5, T-bet, IL-17A, FoxP3, TLR-4, IL-8, IL-1β and IL-6) and Luminex (IFNγ, IL-5 and IL-17A) were used to quantify pro-inflammatory responses.

Results: Nasal polyps and contiguous non-polypoidal sinonasal mucosa from CRSwNP patients displayed a very similar pro-inflammatory profile. When stimulated with SEB, nasal polyps displayed a Th2/Th17 mediated response when compared to controls.

Conclusions: In CRSwNP, nasal polyps and non-polypoidal sinonasal mucosa from the same patient displayed a similar pro-inflammatory profile skewed towards the Th2/Th17 pathway in nasal polyps following SEB stimulation, with evidence of disordered bacterial clearance. These factors may contribute to enhanced survival of bacteria and development of a chronic inflammatory milieu, potentially driving new polyp formation and recurrence following surgical removal.

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More information

Submitted date: 19 April 2019
Accepted/In Press date: 17 May 2019
Published date: 1 October 2019
Additional Information: Winner of Basic Scientific Research Prize. Proceedings of the 27th Congress of the European Rhinologic Society, London, April 2018.
Keywords: chronic rhinosinusitis, immunology, Inflammation, Nasal polyps

Identifiers

Local EPrints ID: 431132
URI: https://eprints.soton.ac.uk/id/eprint/431132
ISSN: 0300-0729
PURE UUID: dfcc5ee6-f950-4799-97fe-67302a9a16f7
ORCID for Sylvia Pender: ORCID iD orcid.org/0000-0001-6332-0333
ORCID for Rami Salib: ORCID iD orcid.org/0000-0002-6753-7844

Catalogue record

Date deposited: 24 May 2019 16:30
Last modified: 29 Oct 2019 01:56

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