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Proteomics of bronchial biopsies: galectin-3 as a predictive biomarker of airway remodelling modulation in omalizumab-treated severe asthma patients.

Abstract
Asthma is a chronic inflammatory disease. Reticular basement membrane (RBM) thickening is considered feature of airway remodelling (AR) particularly in severe asthma (SA). Omalizumab, mAb to IgE is effective in SA and can modulate AR. Herein we describe protein profiles of bronchial biopsies to detect biomarkers of anti-IgE effects on AR and to explain potential mechanisms/pathways. We defined the bronchial biopsy protein profiles, before and after treatment. Unsupervised clustering of baseline proteomes resulted in very good agreement with the morphometric analysis of AR. Protein profiles of omalizumab responders (ORs) were significantly different from those of non-omalizumab responders (NORs). The major differences between ORs and NORs lied to smooth muscle and extra cellular matrix proteins. Notably, an IgE-binding protein (galectin-3) was reliable, stable and predictive biomarker of AR modulation. Omalizumab down-regulated bronchial smooth muscle proteins in SA. These findings suggest that omalizumab may exert disease-modifying effects on remodelling components.
AuthorsPierluigi Mauri, Anna Maria Riccio, Rossana Rossi, Dario Di Silvestre, Louise Benazzi, Laura De Ferrari, Roberto Walter Dal Negro, Stephen T Holgate, Giorgio Walter Canonica
JournalImmunology letters (Immunol Lett) Vol. 162 Issue 1 Pt A Pg. 2-10 (Nov 2014) ISSN: 1879-0542 [Electronic] Netherlands
PMID25194755 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Asthmatic Agents
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Galectin 3
  • Proteome
  • Omalizumab
Topics
  • Adult
  • Airway Remodeling
  • Anti-Asthmatic Agents (therapeutic use)
  • Antibodies, Anti-Idiotypic (therapeutic use)
  • Antibodies, Monoclonal, Humanized (therapeutic use)
  • Asthma (drug therapy, metabolism, pathology)
  • Biomarkers (metabolism)
  • Biopsy
  • Bronchi (metabolism, pathology)
  • Cluster Analysis
  • Female
  • Galectin 3 (metabolism)
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Odds Ratio
  • Omalizumab
  • Prognosis
  • Protein Interaction Maps
  • Proteome
  • Proteomics
  • Severity of Illness Index
  • Treatment Outcome

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