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Expression of eosinophil ? chain-signaling cytokines receptors, outer-membrane integrins, and type 2 inflammation biomarkers in severe non-allergic eosinophilic asthma.


ABSTRACT: BACKGROUND:Severe non-allergic eosinophilic asthma (SNEA) is a rare asthma phenotype associated with severe clinical course, frequent exacerbations, and resistance to therapy, including high steroid doses. The key feature is type 2 inflammation with predominant airway eosinophilia. Eosinophil maturation, activation, survivability, and recruitment are mainly induced by interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) through their receptors on eosinophil surface and related with integrins activation states. The aim of the study was to estimate the expression of eosinophil ? chain-signaling cytokines receptors, outer-membrane integrins, and serum-derived type 2 inflammation biomarkers in SNEA. METHODS:We examined 8 stable SNEA patients with high inhaled steroid doses, 12 steroid-free patients with non-severe allergic asthma (AA), 12 healthy subjects (HS). Blood eosinophils were isolated using Ficol gradient centrifugation and magnetic separation. Eosinophils were lysed, and mRNA was isolated. Gene expressions of IL-5R?, IL-3R?, GM-CSFR?, and ?4?1, ?M?2 integrins were analyzed using quantitative real-time reverse transcription polymerase chain reaction. Type 2 inflammation activity was evaluated measuring exhaled nitric oxide concentration (FeNO) collected with the electrochemical sensing device. Serum IL-5, IL-3, GM-CSF, periostin, chemokine ligand (CCL) 17 and eotaxin concentrations were assessed by enzyme-linked immunosorbent assay. RESULTS:Eosinophils from SNEA patients demonstrated significantly increased gene expression of IL-3R?, IL-5R? and GM-CSFR? as well as ?4, ?1 and ?M integrin subunits compared with the AA group. The highest IL-5 serum concentration was in the SNEA group; it significantly differed compared with AA and HS. GM-CSF serum levels were similar in the SNEA and AA groups and were significantly lower in the HS group. No differences in serum IL-3 concentration were found among all groups. Furthermore, serum levels of eotaxin, CCL17 and FeNO, but not periostin, differed in all groups, with the highest levels in SNEA patients. CONCLUSIONS:Eosinophil demonstrated higher expression of IL-3, IL-5, GM-CSF ?-chain receptors and ?4, ?1, ?M integrins subunits in SNEA compared with the AA group. Additionally, SNEA patients had increased serum levels of IL-5, eotaxin and CCL-17. TRIAL REGISTRATION:ClinicalTrials.gov Identifier NCT03388359.

SUBMITTER: Kalinauskaite-Zukauske V 

PROVIDER: S-EPMC6706886 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Expression of eosinophil β chain-signaling cytokines receptors, outer-membrane integrins, and type 2 inflammation biomarkers in severe non-allergic eosinophilic asthma.

Kalinauskaite-Zukauske Virginija V   Januskevicius Andrius A   Janulaityte Ieva I   Miliauskas Skaidrius S   Malakauskas Kestutis K  

BMC pulmonary medicine 20190822 1


<h4>Background</h4>Severe non-allergic eosinophilic asthma (SNEA) is a rare asthma phenotype associated with severe clinical course, frequent exacerbations, and resistance to therapy, including high steroid doses. The key feature is type 2 inflammation with predominant airway eosinophilia. Eosinophil maturation, activation, survivability, and recruitment are mainly induced by interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF) through their receptors on eosinop  ...[more]

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