title: 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.
authors.affiliation: Institute for Biomedical Technologies (ITB-CNR), Milan, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Mauri
authors.affiliation: Allergy and Respiratory Diseases Unit, Dpt. of Internal Medicine, University of Genoa, IRCCS-IST AOU San Martino, Genoa, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Riccio
authors.affiliation: Institute for Biomedical Technologies (ITB-CNR), Milan, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Institute for Biomedical Technologies (ITB-CNR), Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Di Silvestre
authors.affiliation: Institute for Biomedical Technologies (ITB-CNR), Milan, Italy.
authors.forename: Louise
authors.initials: L
authors.lastname: Benazzi
authors.affiliation: Allergy and Respiratory Diseases Unit, Dpt. of Internal Medicine, University of Genoa, IRCCS-IST AOU San Martino, Genoa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Ferrari
authors.affiliation: CMS, Verona, Italy.
authors.forename: Roberto Walter
authors.initials: RW
authors.lastname: Dal Negro
authors.affiliation: Inflammation, Infection and Immunity Division, Sir Henry Wellcome Laboratories, Mail Point 810, Level F, South Block, Southampton General Hospital, Southampton SO16 6YD, UK.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.affiliation: Allergy and Respiratory Diseases Unit, Dpt. of Internal Medicine, University of Genoa, IRCCS-IST AOU San Martino, Genoa, Italy. Electronic address: canonica@unige.it.
authors.forename: Giorgio Walter
authors.initials: GW
authors.lastname: Canonica
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology*; D016000:Cluster Analysis; D005260:Female; D037502:Galectin 3 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000069444:Omalizumab; D011379:Prognosis; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D037502:Galectin 3; D020543:Proteome; D000069444:Omalizumab
keywords: Galectin-3; Interactome; Omalizumab; Proteomics analysis; Severe asthma