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Citrullinated histone H3, a marker of extracellular trap formation, is increased
in blood of stable asthma patients
#MMPMID32685129
Kuczia P
; Zuk J
; Iwaniec T
; Soja J
; Dropinski J
; Malesa-Wlodzik M
; Zareba L
; Bazan JG
; Undas A
; Bazan-Socha S
Clin Transl Allergy
2020[]; 10
(?): 31
PMID32685129
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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 ?. For
statistical analysis, Mann-Whitney U-test, ?(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) (??=?0.37 [95% CI 0.24-0.50]) and residual volume (??=?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 (??=?0.31 [95% CI 0.19-0.44]) and
monocytes (??=?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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