Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients.
Asthma
Citrullination
Extracellular traps
Histone H3
Journal
Clinical and translational allergy
ISSN: 2045-7022
Titre abrégé: Clin Transl Allergy
Pays: England
ID NLM: 101576043
Informations de publication
Date de publication:
2020
2020
Historique:
received:
08
04
2020
accepted:
19
06
2020
entrez:
21
7
2020
pubmed:
21
7
2020
medline:
21
7
2020
Statut:
epublish
Résumé
Emerging data indicates that extracellular traps (ETs), structures formed by various immune cell types, may contribute to the pathology of noninfectious inflammatory diseases. Histone hypercitrullination is an important step in ETs formation and citrullinated histone H3 (H3cit) is considered a novel and specific biomarker of that process. In the present study we have evaluated circulating H3cit in stable asthmatics and investigated its relationship with asthma severity, pulmonary function and selected blood and bronchoalveolar lavage (BAL) biomarkers. In 60 white adult stable asthmatics and 50 well-matched controls we measured serum levels of H3cit. In asthmatics we also performed bronchoscopy with BAL. We analyzed blood and BAL biomarkers, including interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A and interferon γ. For statistical analysis, Mann-Whitney U-test, χ Asthma was characterized by elevated circulating H3cit (17.49 [11.25-22.58] vs. 13.66 [8.66-18.87] ng/ml, p = 0.03). In asthmatics positive associations were demonstrated between serum H3cit and lung function variables, including total lung capacity (TLC) (β = 0.37 [95% CI 0.24-0.50]) and residual volume (β = 0.38 [95% CI 0.25-0.51]). H3cit was increased in asthma patients receiving systemic steroids (p = 0.02), as well as in subjects with BAL eosinophilia above 144 cells/ml (p = 0.02). In asthmatics, but not in controls, circulating H3cit correlated well with number of neutrophils (β = 0.31 [95% CI 0.19-0.44]) and monocytes (β = 0.42 [95% CI 0.29-0.55]) in peripheral blood. Furthermore, BAL macrophages, BAL neutrophils, TLC, high-sensitivity C-reactive protein, Il-12p70 and bronchial obstruction degree were independent determinants of H3cit in a multivariate linear regression model. Asthma is characterized by increased circulating H3cit likely related to the enhanced lung ETs formation. Inhibition of ETs might be a therapeutic option in selected asthma phenotypes, such as neutrophilic asthma.
Sections du résumé
BACKGROUND
BACKGROUND
Emerging data indicates that extracellular traps (ETs), structures formed by various immune cell types, may contribute to the pathology of noninfectious inflammatory diseases. Histone hypercitrullination is an important step in ETs formation and citrullinated histone H3 (H3cit) is considered a novel and specific biomarker of that process. In the present study we have evaluated circulating H3cit in stable asthmatics and investigated its relationship with asthma severity, pulmonary function and selected blood and bronchoalveolar lavage (BAL) biomarkers.
METHODS
METHODS
In 60 white adult stable asthmatics and 50 well-matched controls we measured serum levels of H3cit. In asthmatics we also performed bronchoscopy with BAL. We analyzed blood and BAL biomarkers, including interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12p70, IL-17A and interferon γ. For statistical analysis, Mann-Whitney U-test, χ
RESULTS
RESULTS
Asthma was characterized by elevated circulating H3cit (17.49 [11.25-22.58] vs. 13.66 [8.66-18.87] ng/ml, p = 0.03). In asthmatics positive associations were demonstrated between serum H3cit and lung function variables, including total lung capacity (TLC) (β = 0.37 [95% CI 0.24-0.50]) and residual volume (β = 0.38 [95% CI 0.25-0.51]). H3cit was increased in asthma patients receiving systemic steroids (p = 0.02), as well as in subjects with BAL eosinophilia above 144 cells/ml (p = 0.02). In asthmatics, but not in controls, circulating H3cit correlated well with number of neutrophils (β = 0.31 [95% CI 0.19-0.44]) and monocytes (β = 0.42 [95% CI 0.29-0.55]) in peripheral blood. Furthermore, BAL macrophages, BAL neutrophils, TLC, high-sensitivity C-reactive protein, Il-12p70 and bronchial obstruction degree were independent determinants of H3cit in a multivariate linear regression model.
CONCLUSIONS
CONCLUSIONS
Asthma is characterized by increased circulating H3cit likely related to the enhanced lung ETs formation. Inhibition of ETs might be a therapeutic option in selected asthma phenotypes, such as neutrophilic asthma.
Identifiants
pubmed: 32685129
doi: 10.1186/s13601-020-00337-8
pii: 337
pmc: PMC7354860
doi:
Types de publication
Journal Article
Langues
eng
Pagination
31Informations de copyright
© The Author(s) 2020.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare that they have no competing interests.
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