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Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry

Weitoft, Maria LU ; Müller, Catharina LU ; Åhrman, Emma LU ; Bjermer, Leif LU ; Hoffmann, Hans Jürgen ; Erjefält, Jonas LU and Westergren-Thorsson, Gunilla LU (2019) In American Journal of Pathology 189(12). p.2358-2365
Abstract

A proportion of patients with severe asthma (SA) show poor responses to traditional asthma medications; however, it remains unknown why some patients remain persistently symptomatic. Our objective was to explore the use of laser-capture microdissection of specific epithelial structures combined with quantitative data-independent acquisition mass spectrometry to elucidate differences in protein composition in patients with SA with varying symptom control. Unbiased label-free quantitative proteome analyses were performed on laser-capture–microdissected areas of specific epithelial structures from patients with SA with varying degrees of symptom control. A total of 1993 stable SA and 1652 symptomatic SA proteins in normal epithelium and... (More)

A proportion of patients with severe asthma (SA) show poor responses to traditional asthma medications; however, it remains unknown why some patients remain persistently symptomatic. Our objective was to explore the use of laser-capture microdissection of specific epithelial structures combined with quantitative data-independent acquisition mass spectrometry to elucidate differences in protein composition in patients with SA with varying symptom control. Unbiased label-free quantitative proteome analyses were performed on laser-capture–microdissected areas of specific epithelial structures from patients with SA with varying degrees of symptom control. A total of 1993 stable SA and 1652 symptomatic SA proteins in normal epithelium and 1458 stable SA and 1647 symptomatic SA proteins in metaplastic epithelium were quantified. When comparing proteome profiles based on symptom control, 33 proteins in patients with stable SA (≥twofold change; P ≤ 0.05) and 13 proteins in patients with persistently symptomatic SA (≥twofold change; P ≤ 0.05) were enriched significantly. When comparing proteome profiles based on epithelial status, 21 proteins in normal epithelium (≥twofold change; P ≤ 0.05) and 6 proteins in metaplastic epithelium (≥twofold change; P ≤ 0.05) were enriched significantly. New treatment strategies are needed for patients with severe asthma and exploratory studies of unbiased nature such as this may help when searching for new mechanisms and potential targets involved in the disease pathology.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
189
issue
12
pages
8 pages
publisher
American Society for Investigative Pathology
external identifiers
  • scopus:85075215307
  • pmid:31761031
ISSN
0002-9440
DOI
10.1016/j.ajpath.2019.08.003
language
English
LU publication?
yes
id
753ff78e-d538-463f-91a4-5a6da4605912
date added to LUP
2019-12-04 13:23:07
date last changed
2020-05-26 05:36:22
@article{753ff78e-d538-463f-91a4-5a6da4605912,
  abstract     = {<p>A proportion of patients with severe asthma (SA) show poor responses to traditional asthma medications; however, it remains unknown why some patients remain persistently symptomatic. Our objective was to explore the use of laser-capture microdissection of specific epithelial structures combined with quantitative data-independent acquisition mass spectrometry to elucidate differences in protein composition in patients with SA with varying symptom control. Unbiased label-free quantitative proteome analyses were performed on laser-capture–microdissected areas of specific epithelial structures from patients with SA with varying degrees of symptom control. A total of 1993 stable SA and 1652 symptomatic SA proteins in normal epithelium and 1458 stable SA and 1647 symptomatic SA proteins in metaplastic epithelium were quantified. When comparing proteome profiles based on symptom control, 33 proteins in patients with stable SA (≥twofold change; P ≤ 0.05) and 13 proteins in patients with persistently symptomatic SA (≥twofold change; P ≤ 0.05) were enriched significantly. When comparing proteome profiles based on epithelial status, 21 proteins in normal epithelium (≥twofold change; P ≤ 0.05) and 6 proteins in metaplastic epithelium (≥twofold change; P ≤ 0.05) were enriched significantly. New treatment strategies are needed for patients with severe asthma and exploratory studies of unbiased nature such as this may help when searching for new mechanisms and potential targets involved in the disease pathology.</p>},
  author       = {Weitoft, Maria and Müller, Catharina and Åhrman, Emma and Bjermer, Leif and Hoffmann, Hans Jürgen and Erjefält, Jonas and Westergren-Thorsson, Gunilla},
  issn         = {0002-9440},
  language     = {eng},
  number       = {12},
  pages        = {2358--2365},
  publisher    = {American Society for Investigative Pathology},
  series       = {American Journal of Pathology},
  title        = {Comparison of Normal and Metaplastic Epithelium in Patients with Stable versus Persistently Symptomatic Severe Asthma Using Laser-Capture Microdissection and Data-Independent Acquisition–Mass Spectrometry},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2019.08.003},
  doi          = {10.1016/j.ajpath.2019.08.003},
  volume       = {189},
  year         = {2019},
}