Biomarker discovery in asthma and COPD by proteomic approaches

Rossi, Rossana; Palma, Antonella De; Benazzi, Louise; Riccio, Anna Maria; Canonica, Giorgio Walter; Mauri, Pierluigi

doi:10.1002/prca.201300108

Cited by 24 publications

(21 citation statements)

References 82 publications

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“…In this context, current advances in proteomics, mainly those based on mass spectrometry, facilitate the discovery-driven studies of new biomarkers in respiratory diseases and improve the clinical reliability of biomarkers for asthma [20]. …”

Section: Discussionmentioning

confidence: 99%

Galectin-3: an early predictive biomarker of modulation of airway remodeling in patients with severe asthma treated with omalizumab for 36 months

Riccio

Mauri²,

Ferrari

et al. 2017

Clin Transl Allergy

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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.ResultsAfter 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13601-017-0143-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Galectin-3: an early predictive biomarker of modulation of airway remodeling in patients with severe asthma treated with omalizumab for 36 months

Riccio

Mauri²,

Ferrari

et al. 2017

Clin Transl Allergy

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“…A review has recently outlined the proteomic methods currently applied with a view to the discovery of biomarkers for asthma and COPD [94]. In childhood asthma, the proteomic analysis of EBC was able to discriminate between different protein profiles in patients and healthy controls [95].…”

Section: Promising Approaches and Future Researchmentioning

confidence: 99%

Childhood asthma biomarkers: present knowledge and future steps

Moschino

Zanconato

Bozzetto

et al. 2015

Paediatric Respiratory Reviews

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“…The so-called “omics” sciences such as genomics and proteomics are providing new tools to facilitate discovery-driven studies on new and reliable biomarkers that can predict response to therapy, help identify patients who are more suitable for a given treatment and provide a focus for the development of targeted therapies 16. New treatments such as biological therapies are now available that modify specific pathogenic mechanisms based on precise genotype characterization in the individual patient.…”

Section: Introductionmentioning

confidence: 99%

Targeted therapy in severe asthma today: focus on immunoglobulin E

Pelaia¹,

Canonica²,

Matucci³

et al. 2017

DDDT

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Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard “one size fits all” approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma.

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Biomarker discovery in asthma and COPD by proteomic approaches

Cited by 24 publications

References 82 publications

Galectin-3: an early predictive biomarker of modulation of airway remodeling in patients with severe asthma treated with omalizumab for 36 months

Galectin-3: an early predictive biomarker of modulation of airway remodeling in patients with severe asthma treated with omalizumab for 36 months

Childhood asthma biomarkers: present knowledge and future steps

Targeted therapy in severe asthma today: focus on immunoglobulin E

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