Using Periostin as a Biomarker in the Treatment of Asthma

Abstract

Periostin acts both as an extracellular matrix protein belonging to the fasciclin family and as a matricellular protein functioning in cell activation by binding to its receptors on the cell surface. It has been established that periostin is a downstream molecule of interleukin (IL)-13, a signature type 2 cytokine, and that periostin plays an important role in the pathogenesis of allergic diseases, including asthma. Based on these findings, much attention has been paid to periostin as a biomarker useful in the treatment of asthma. Periostin is a surrogate biomarker for type 2 immunity; it has been shown that serum periostin can predict the efficacy of anti-IL-13 antibodies (lebrikizumab) and anti-IgE antibodies (omalizumab), and that this usefulness can be potentially expanded to other type 2 antagonists. Moreover, it has been shown that periostin is not a simple surrogate biomarker for type 2 immunity; periostin-high asthma patients have several unique characteristics, including eosinophilia, high fraction of nitric oxide, aspirin intolerance, nasal disorders, and late onset. These characteristics are likely to be correlated with the involvement of periostin in the tissue remodeling of asthma. Periostin is also associated with hyporesponsiveness to inhaled corticosteroids, probably reflecting tissue remodeling. Thus, periostin has 2 characteristics as a biomarker for early diagnosis of asthma: surrogate biomarkers for type 2 immunity and tissue remodeling. Based on these characteristics, we will be able to apply serum periostin to treatment of asthma.

Periostin in bronchial asthma – a brief update

“…lebrikizumab (anti-IL-13 antibody) [13]. This final feature is also supported by the results of studies which demonstrated a higher efficiency of lebrikizumab therapy in asthmatic patients with increased periostin serum level, compared to patients with a low level of serum periostin [32,33].…”

“…Thus, an increased periostin level associated with eosinophilia and Th2 mediated inflammation is seen in a specific type of bronchial asthma. Activated Th2 cells are able to produce several inflammatory cytokines, such as IL-4 and IL-13, as the main activators of periostin gene expression in the bronchial wall in asthmatic disease [13,19].…”

“…Recent data have shown periostin intervention in lung idiopathic diseases and in characteristic bronchial inflammatory and remodeling processes of asthmatic disease, by interaction with other extracellular matrix molecules, at the epithelial-connective tissue interface [12,13].…”

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

“…Periostin is a protein that acts as an extracellular and matricellular matrix protein and its production is induced by IL-13 and IL-4 which are both cytokines that figure prominently in Th2 inflammation. 57 Immunohistochemical studies have identified periostin deposition on the basement membrane of individuals with asthma, suggesting that it contributes to sub-epithelial fibrosis in asthma. 57 Periostin does not appear to be as a useful biomarker in childhood asthma because periostin levels are high normally in growing children such that differences between healthy children and those with asthma is comparatively small or not significant.…”

“…57 Immunohistochemical studies have identified periostin deposition on the basement membrane of individuals with asthma, suggesting that it contributes to sub-epithelial fibrosis in asthma. 57 Periostin does not appear to be as a useful biomarker in childhood asthma because periostin levels are high normally in growing children such that differences between healthy children and those with asthma is comparatively small or not significant. 58 Although it might be a useful biomarker of response to drugs that might be commercialized in the future, there is currently no clinically available commercial assay for periostin.…”