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Pulmonary – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
An analysis of gene expression in bronchial biopsies from the same patients has shown that the gene for periostin is one of those most highly expressed in the Th2 high population. Periostin is a matricellular protein that has been identified as a component of subepithelial fibrosis in bronchial asthma. Serum periostin was subsequently shown to perform well as a predictive biomarker of the response to the anti-IL-13 monoclonal antibody Lebrikizumab and as a prognostic and predictive biomarker of a response to Omalizumab in patients with allergic asthma. However, higher serum levels of periostin were not associated with an increased risk of severe exacerbations in a recent cohort study and failed as a predictive biomarker in the phase 3 studies of Lebrikizumab in moderate-severe asthma. Serum levels are higher following perturbations of bone or teeth, in children and in those of Chinese descent, so there is the potential for non-type-2 airway inflammation-related factors to limit the predictive and prognostic value of periostin.
Osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Ippokratis Pountos, Peter V. Giannoudis
Periostin is a matricellular Gla-containing protein expressed in collagen-rich tissues like bone. It was initially considered to derive specifically from periosteum; however, recent data suggest it is involved in heart morphogenesis and lung and renal diseases, as well as vascular smooth muscle cells. Defects in periostin result in defects in cortical architecture and low mineral density (35). In a recent study, high serum periostin levels were found to be independently associated with increased fracture risk in postmenopausal women (36).
Biologics in allergic disease
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Tara V. Saco, Farnaz Tabatabaian
All monoclonal biologics approved to date target Th2 asthma. Biomarkers used to identify Th2 asthma include fractional exhaled nitric oxide (FeNO), peripheral eosinophilia, blood periostin level, and presence of allergen-specific IgE. Poorly controlled asthma with recurrent exacerbations is associated with increased blood or sputum eosinophils. It is challenging clinically to measure sputum eosinophils. However, obtaining blood eosinophils is relatively simple. Epithelial cells lining the alveoli express high quantity of inducible nitric oxide synthase (iNOS). IL-4 and -13 upregulate the expression of iNOS and hence the production of nitric oxide (NO) [34,35]. Elevated FeNO is a noninvasive biomarker for T2 inflammation. Periostin is increased in the presence of IL-13 [15]. The clinical use of these biomarkers is an indication of upregulation of Th2 inflammatory mediators and possible responsiveness to these biologic agents. There are no head-to-head trials comparing these agents. Factors that may play a role in selecting a biologic agent include ease of therapy, route and frequency of the medication, out-of-pocket cost and confounding atopic comorbidities, such as atopic dermatitis, nasal polyps, food allergy, and allergic rhinoconjunctivitis.
The functional role and the clinical application of periostin in chronic rhinosinusitis
Published in Expert Review of Clinical Immunology, 2023
Kenji Izuhara, Shigeharu Fujieda, Nobuo Ohta
The functional mechanism of how periostin is involved in tissue remodeling or clinical severity has not been enough understood. One of the reasons would be that it is difficult to confirm using animal models the functional significance of periostin in the formation of nasal polyps. However, a lot of evidence based on mouse models of other periostin-related diseases supports its significance, and several underlying mechanisms involving periostin have been proposed. These results suggest that periostin is a promising therapeutic target for CRS. Thus far, several periostin inhibitors, including cilengitide, have been administered to mice, showing efficacy sufficient to improve periostin-related pathogenesis [83,86–91]. We have already administered CP4715, a low-molecular compound to inhibit the interaction between periostin and its receptor, αVβ3 integrin, to mouse models of both pulmonary fibrosis and atopic dermatitis, showing good efficacies [77,79,92]. CP4715, which was developed as an integrin inhibitor, has a tetrahydropyrimidin-2-yl-amino moiety at the N terminus and a benzoyl moiety at the center [93–96]. Further studies aimed at establishing periostin as a therapeutic target for CRS are hoped for soon.
Periostin aggravates the early phase of traumatic brain injury via the MAPK/ERK pathway
Published in Neurological Research, 2022
Yongke Zheng, Longhuan Zeng, Xiaoqiao Dong, Quan Du, Yue Gao
Periostin is a 93-kDa novel ECM protein that is involved in the regulation of cell adhesion, cell differentiation, and organization of the ECM [5]. Previous studies have identified its potential involvement in a number of physiological and pathological processes, including the development of bones and teeth, cancer cell invasion and metastasis, and myocardial damage after acute myocardial infarction [18–21]. Periostin has also been identified as a secreted matricellular protein with emerging importance in the BBB. However, the role of periostin in the early phase of TBI remains unknown. Here, we showed that periostin expression increased in TBI-treated rats and may therefore be involved in the early phase of TBI. In addition, we found that R-periostin aggravated post-TBI neurobehavioral and limb function impairments, and brain edema by evaluation of neuroscore, limb function as well as brain water content. Furthermore, the data in this study showed that periostin could exacerbate the effects of TBI in the late phase.
Relationship between sputum periostin level and inflammatory asthma phenotypes in Egyptian patients
Published in Journal of Asthma, 2021
Maged Mohamed Refaat, Eman El Sayed, Wael Abd El-Fattah, Amr Helmy Elbanna, Hoda Mohamed El Sayed
Biomarkers seem a promising tool that may aid a more precise subtyping of asthma and more targeted therapies. Periostin is one of the biomarkers currently investigated. It is a matricellular protein that is expressed by airway epithelial cells and lung fibroblast. It is a downstream molecule of interleukin (IL)-4 and IL-13, which are signature cytokines of type 2 immune responses (6). Recent studies have suggested a role of periostin in the pathogenesis, treatment, and phenotyping of asthma (7–11). It was found to promote subepithelial fibrosis, prolong Th2/eosinophilic inflammation, aggravate airway remodeling and associated with increased number of eosinophils in the airways. Another study concluded that serum periostin level correlates modestly with other biomarkers of type-2 inflammation, such as blood eosinophilic count, serum IgE, and FeNO, thus can be considered as a comparable or complementary biomarker (11). Nevertheless, serum periostin is subjected to some confounding factors which may interfere with its accurate reflection of the level of production in the airways such as bone turnover in children (12). Moreover, a large population-based cohort study did not find any differences in median serum periostin levels between different groups (13).