Plasma proteome changes linked to late phase response after inhaled allergen challenge in asthmatics
Weitoft, Maria LU ; Kadefors, Måns LU ; Stenberg, Henning LU ; Tufvesson, Ellen LU ; Diamant, Zuzana LU ; Rolandsson Enes, Sara LU
; Bjermer, Leif
LU
; Rosmark, Oskar
LU
and Westergren-Thorsson, Gunilla
LU
(2022)
In Respiratory Research
23(1).
- Abstract
Background: A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge. Methods: Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the... (More)
Background: A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge. Methods: Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays were analyzed using linear mixed models. Results: Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated proteins were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes. Conclusions: Allergic reactions to inhaled allergens in asthmatic subjects were associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma.
(Less)
- author
- Weitoft, Maria
LU
; Kadefors, Måns
LU
; Stenberg, Henning
LU
; Tufvesson, Ellen
LU
; Diamant, Zuzana
LU
; Rolandsson Enes, Sara
LU
; Bjermer, Leif
LU
; Rosmark, Oskar
LU
and Westergren-Thorsson, Gunilla
LU
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Airway inflammation, Allergic asthma, Coagulation, Mass spectrometry, Protease inhibition
- in
- Respiratory Research
- volume
- 23
- issue
- 1
- article number
- 50
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:35248034
- scopus:85125860485
- ISSN
- 1465-9921
- DOI
- 10.1186/s12931-022-01968-0
- language
- English
- LU publication?
- yes
- id
- 757b8acf-f5bc-4863-a31b-3705c0161a61
- date added to LUP
- 2022-04-26 10:50:00
- date last changed
- 2024-06-14 14:48:40
@article{757b8acf-f5bc-4863-a31b-3705c0161a61,
abstract = {{<p>Background: A subset of individuals with allergic asthma develops a late phase response (LPR) to inhaled allergens, which is characterized by a prolonged airway obstruction, airway inflammation and airway hyperresponsiveness. The aim of this study was to identify changes in the plasma proteome and circulating hematopoietic progenitor cells associated with the LPR following inhaled allergen challenge. Methods: Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed by mass spectrometry and immunosorbent assays. Peripheral blood mononuclear cells were analyzed by flow cytometry. Mass spectrometry data were analyzed using a linear regression to model the relationship between airway obstruction during the LPR and plasma proteome changes. Data from immunosorbent assays were analyzed using linear mixed models. Results: Out of 396 proteins quantified in plasma, 150 showed a statistically significant change 23 h post allergen challenge. Among the most upregulated proteins were three protease inhibitors: alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Altered levels of 13 proteins were associated with the LPR, including increased factor XIII A and decreased von Willebrand factor. No relationship was found between the LPR and changes in the proportions of classical, intermediate, and non-classical monocytes. Conclusions: Allergic reactions to inhaled allergens in asthmatic subjects were associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors showed the largest changes, likely to influence the inflammatory response. Many of the proteins altered in relation to the LPR are associated with coagulation, highlighting potential mechanistic targets for future treatments of type-2 asthma.</p>}},
author = {{Weitoft, Maria and Kadefors, Måns and Stenberg, Henning and Tufvesson, Ellen and Diamant, Zuzana and Rolandsson Enes, Sara and Bjermer, Leif and Rosmark, Oskar and Westergren-Thorsson, Gunilla}},
issn = {{1465-9921}},
keywords = {{Airway inflammation; Allergic asthma; Coagulation; Mass spectrometry; Protease inhibition}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Respiratory Research}},
title = {{Plasma proteome changes linked to late phase response after inhaled allergen challenge in asthmatics}},
url = {{http://dx.doi.org/10.1186/s12931-022-01968-0}},
doi = {{10.1186/s12931-022-01968-0}},
volume = {{23}},
year = {{2022}},
}