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Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients

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 consid...

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Autores principales: Kuczia, Pawel, Zuk, Joanna, Iwaniec, Teresa, Soja, Jerzy, Dropinski, Jerzy, Malesa-Wlodzik, Marta, Zareba, Lech, Bazan, Jan G., Undas, Anetta, Bazan-Socha, Stanislawa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354860/
https://www.ncbi.nlm.nih.gov/pubmed/32685129
http://dx.doi.org/10.1186/s13601-020-00337-8
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author Kuczia, Pawel
Zuk, Joanna
Iwaniec, Teresa
Soja, Jerzy
Dropinski, Jerzy
Malesa-Wlodzik, Marta
Zareba, Lech
Bazan, Jan G.
Undas, Anetta
Bazan-Socha, Stanislawa
author_facet Kuczia, Pawel
Zuk, Joanna
Iwaniec, Teresa
Soja, Jerzy
Dropinski, Jerzy
Malesa-Wlodzik, Marta
Zareba, Lech
Bazan, Jan G.
Undas, Anetta
Bazan-Socha, Stanislawa
author_sort Kuczia, Pawel
collection PubMed
description 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: 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(2) test, one-way ANCOVA, ROC curve analysis and univariate linear regression were applied. Independent determinants of H3cit were established in a multiple linear regression model. 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: 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.
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spelling pubmed-73548602020-07-13 Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients Kuczia, Pawel Zuk, Joanna Iwaniec, Teresa Soja, Jerzy Dropinski, Jerzy Malesa-Wlodzik, Marta Zareba, Lech Bazan, Jan G. Undas, Anetta Bazan-Socha, Stanislawa Clin Transl Allergy Research 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: 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(2) test, one-way ANCOVA, ROC curve analysis and univariate linear regression were applied. Independent determinants of H3cit were established in a multiple linear regression model. 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: 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. BioMed Central 2020-07-13 /pmc/articles/PMC7354860/ /pubmed/32685129 http://dx.doi.org/10.1186/s13601-020-00337-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kuczia, Pawel
Zuk, Joanna
Iwaniec, Teresa
Soja, Jerzy
Dropinski, Jerzy
Malesa-Wlodzik, Marta
Zareba, Lech
Bazan, Jan G.
Undas, Anetta
Bazan-Socha, Stanislawa
Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients
title Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients
title_full Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients
title_fullStr Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients
title_full_unstemmed Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients
title_short Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients
title_sort citrullinated histone h3, a marker of extracellular trap formation, is increased in blood of stable asthma patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354860/
https://www.ncbi.nlm.nih.gov/pubmed/32685129
http://dx.doi.org/10.1186/s13601-020-00337-8
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