Biomarker framework for chronic airway diseases. Positioning ADAM17 across immune cells in COPD and asthma
Lau, Carin LU
(2026)
In Lund University, Faculty of Medicine Doctoral Dissertation Series
- Abstract
- Chronic obstructive pulmonary disease (COPD) and asthma are heterogeneous respiratory diseases with overlapping symptoms but distinct underlying biology. As both diseases involve dysregulated inflammatory signalling, identifying disease- and compartment-specific pathways and biomarkers could improve diagnosis and treatment. A disintegrin and metalloproteinase 17 (ADAM17) is a key sheddase that influences inflammatory signalling and epithelial injury and repair by cleaving over 90 membrane-bound substrates, this process can be enhanced by phosphorylation of ADAM17 (pADAM17).
The aim of this thesis was to broadly characterise protein-based pathways in COPD and asthma by profiling ADAM17-related markers across airway and systemic... (More) - Chronic obstructive pulmonary disease (COPD) and asthma are heterogeneous respiratory diseases with overlapping symptoms but distinct underlying biology. As both diseases involve dysregulated inflammatory signalling, identifying disease- and compartment-specific pathways and biomarkers could improve diagnosis and treatment. A disintegrin and metalloproteinase 17 (ADAM17) is a key sheddase that influences inflammatory signalling and epithelial injury and repair by cleaving over 90 membrane-bound substrates, this process can be enhanced by phosphorylation of ADAM17 (pADAM17).
The aim of this thesis was to broadly characterise protein-based pathways in COPD and asthma by profiling ADAM17-related markers across airway and systemic compartments, and across relevant airway cell subsets. ADAM17 and pADAM17 localisation and expression were assessed in bronchial epithelium, bronchoalveolar lavage (BAL) cytospins, and circulating immune cells. Soluble ADAM17-related substrates were quantified in BAL fluid and blood, as well as in sputum and nasal lavage fluid in asthma, all measures were compared with the respective controls. To test the clinical applicability of assessing ADAM17, changes were also investigated after an exercise intervention.
ADAM17-associated substrate patterns showed more differences relative to controls in COPD BAL fluid than in asthma BAL fluid, and immunofluorescence staining suggested disease-related differences in epithelial ADAM17–pADAM17 localisation (Papers I–II). Given the more frequent substrate differences observed in COPD, exercise-related changes in ADAM17 and pADAM17 cell subsets were evaluated and found to be consistent with a redistribution of immune-cell phenotypes post-exercise, particularly in males (Paper III). Since ADAM17-defined immune-cell subsets differed between COPD and controls, additional cell subsets were profiled using cell-type-resolved GeoMx proteomics, revealing opposing disease–control shifts in cell death-related proteins that were generally decreased in COPD (particularly in neutrophils) but increased in asthma relative to controls (Paper IV).
In conclusion, ADAM17 profiles and immune cell subsets, in general, differ in chronic respiratory diseases compared to both controls, and also between diseases. The ADAM17 profile also tends to be sex-dependent and can shift during therapeutic interventions, such as exercise-associated changes seen in COPD. ADAM17-related cellular phenotypes and soluble substrate patterns can add value as part of a broader biomarker strategy for understanding and phenotyping COPD and asthma. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2463110d-4f49-45c2-8a86-dbd7865ddda5
- author
- Lau, Carin
LU
- supervisor
- opponent
-
- Professor PhD FRSB FBPhS FEAACI FERS Adcock, Ian M, National Heart and Lung Institute, Imperial College London, UK
- organization
- publishing date
- 2026
- type
- Thesis
- publication status
- published
- subject
- keywords
- ADAM17, Ectodomain shedding, COPD, Asthma, BALF, Peripheral blood cells, Biomarkers, Exercise intervention, Sex differences
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2026:42
- pages
- 94 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
- defense date
- 2026-03-26 09:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-840-5
- project
- Biomarker framework for chronic airway diseases. Positioning ADAM17 across immune cells in COPD and asthma
- language
- English
- LU publication?
- yes
- id
- 2463110d-4f49-45c2-8a86-dbd7865ddda5
- date added to LUP
- 2026-02-27 10:28:36
- date last changed
- 2026-02-28 09:09:22
@phdthesis{2463110d-4f49-45c2-8a86-dbd7865ddda5,
abstract = {{Chronic obstructive pulmonary disease (COPD) and asthma are heterogeneous respiratory diseases with overlapping symptoms but distinct underlying biology. As both diseases involve dysregulated inflammatory signalling, identifying disease- and compartment-specific pathways and biomarkers could improve diagnosis and treatment. A disintegrin and metalloproteinase 17 (ADAM17) is a key sheddase that influences inflammatory signalling and epithelial injury and repair by cleaving over 90 membrane-bound substrates, this process can be enhanced by phosphorylation of ADAM17 (pADAM17).<br/><br/>The aim of this thesis was to broadly characterise protein-based pathways in COPD and asthma by profiling ADAM17-related markers across airway and systemic compartments, and across relevant airway cell subsets. ADAM17 and pADAM17 localisation and expression were assessed in bronchial epithelium, bronchoalveolar lavage (BAL) cytospins, and circulating immune cells. Soluble ADAM17-related substrates were quantified in BAL fluid and blood, as well as in sputum and nasal lavage fluid in asthma, all measures were compared with the respective controls. To test the clinical applicability of assessing ADAM17, changes were also investigated after an exercise intervention.<br/><br/>ADAM17-associated substrate patterns showed more differences relative to controls in COPD BAL fluid than in asthma BAL fluid, and immunofluorescence staining suggested disease-related differences in epithelial ADAM17–pADAM17 localisation (Papers I–II). Given the more frequent substrate differences observed in COPD, exercise-related changes in ADAM17 and pADAM17 cell subsets were evaluated and found to be consistent with a redistribution of immune-cell phenotypes post-exercise, particularly in males (Paper III). Since ADAM17-defined immune-cell subsets differed between COPD and controls, additional cell subsets were profiled using cell-type-resolved GeoMx proteomics, revealing opposing disease–control shifts in cell death-related proteins that were generally decreased in COPD (particularly in neutrophils) but increased in asthma relative to controls (Paper IV).<br/><br/>In conclusion, ADAM17 profiles and immune cell subsets, in general, differ in chronic respiratory diseases compared to both controls, and also between diseases. The ADAM17 profile also tends to be sex-dependent and can shift during therapeutic interventions, such as exercise-associated changes seen in COPD. ADAM17-related cellular phenotypes and soluble substrate patterns can add value as part of a broader biomarker strategy for understanding and phenotyping COPD and asthma.}},
author = {{Lau, Carin}},
isbn = {{978-91-8021-840-5}},
issn = {{1652-8220}},
keywords = {{ADAM17; Ectodomain shedding; COPD; Asthma; BALF; Peripheral blood cells; Biomarkers; Exercise intervention; Sex differences}},
language = {{eng}},
number = {{2026:42}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Biomarker framework for chronic airway diseases. Positioning ADAM17 across immune cells in COPD and asthma}},
url = {{https://lup.lub.lu.se/search/files/243472990/Carin_E._Lau_-_WEBB.pdf}},
year = {{2026}},
}