title: Galectin-3: an early predictive biomarker of modulation of airway remodeling in patients with severe asthma treated with omalizumab for 36 months.
abstract: BACKGROUND
  Bronchial asthma is a heterogeneous disease characterized by three cardinal features: chronic inflammation, variable airflow obstruction, and airway hyperresponsiveness. Asthma has traditionally been defined using nonspecific clinical and physiologic variables that encompass multiple phenotypes and are treated with nonspecific anti-inflammatory therapies. Based on the modulation of airway remodeling after 12 months of anti-immunoglobulin E (IgE) treatment, we identified two phenotypes (omalizumab responder, OR; and non-omalizumab responder, NOR) and performed morphometric analysis of bronchial biopsy specimens. We also found that these two phenotypes were correlated with the presence/absence of galectin-3 (Gal-3) at baseline (i.e., before treatment). The aims of the present study were to investigate the histological and molecular effects of long-term treatment (36 months) with anti-IgE and to analyze the behavior of OR and NOR patients.
  
  
  METHODS
  All patients were treated with the monoclonal antibody anti-IgE omalizumab for 36 months. The bronchial biopsy specimens were evaluated using morphometric, eosinophilic, and proteomic analysis (MudPIT). New data were compared with previous data, and unsupervised cluster analysis of protein profiles was performed.
  
  
  RESULTS
  After 36 months of treatment with omalizumab, reduction of reticular basement membrane (RBM) thickness was confirmed in OR patients (Gal-3-positive at baseline); similarly, the protein profiles (over 500 proteins identified) revealed that, in the OR group, levels of proteins specifically related to fibrosis and inflammation (e.g., smooth muscle and extracellular matrix proteins (including periostin), Gal-3, and keratins decreased by between 5- and 50-fold. Eosinophil levels were consistent with molecular data and decreased by about tenfold less in ORs and increased by twofold to tenfold more in NORs. This tendency was confirmed (p < 0.05) based on both fold change and DAVE algorithms, thus indicating a clear response to anti-IgE treatment in Gal-3-positive patients.
  
  
  CONCLUSIONS
  Our results showed that omalizumab can be considered a disease-modifying treatment in OR. The proteomic signatures confirmed the presence of Gal-3 at baseline to be a biomarker of long-term reduction in bronchial RBM thickness, eosinophilic inflammation, and muscular and fibrotic components in omalizumab-treated patients with severe asthma. Our findings suggest a possible relationship between Gal-3 positivity and improved pulmonary function.
authors.affiliation: Respiratory Diseases and Allergy Unit, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Riccio
authors.affiliation: Proteomics and Metabolomics Unit, Institute for Biomedical Technologies, CNR, Milan, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Mauri
authors.affiliation: Respiratory Diseases and Allergy Unit, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Ferrari
authors.affiliation: Proteomics and Metabolomics Unit, Institute for Biomedical Technologies, CNR, Milan, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Proteomics and Metabolomics Unit, Institute for Biomedical Technologies, CNR, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Di Silvestre
authors.affiliation: Proteomics and Metabolomics Unit, Institute for Biomedical Technologies, CNR, Milan, Italy.
authors.forename: Louise
authors.initials: L
authors.lastname: Benazzi
authors.affiliation: Respiratory Diseases and Allergy Unit, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Chiappori
authors.affiliation: National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, CESFAR, Verona, Italy.
authors.forename: Roberto Walter
authors.initials: RW
authors.lastname: Dal Negro
authors.affiliation: Respiratory Unit, Mater Salutis Hospital, Legnago, Verona Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Micheletto
authors.affiliation: Respiratory Diseases and Allergy Unit, IRCCS AOU San Martino-IST, University of Genoa, Genoa, Italy.|Department of Biomedical Sciences, Personalized Medicine Clinic Asthma and Allergy, Humanitas University, Rozzano, Milan, Italy.
authors.forename: Giorgio Walter
authors.initials: GW
authors.lastname: Canonica
keywords: Airway remodeling; Anti-IgE; Biomarker; Bronchial biopsy; Eosinophils; Galectin-3; Omalizumab; Proteomics; Severe asthma