Periostin as a Biomarker for Type 2 Asthma
Periostin is a protein having two characteristics—an extracellular matrix (ECM) protein important for maintaining tissue or organ structures and in generating fibrosis by binding to other ECM proteins and a matricellular protein transducing intracellular signaling by binding to several integrins on the cell surface. IL-4 and IL-13, signature type 2 cytokines abundantly expressed in the inflamed sites of asthma, induce periostin in several tissue-resident cells—fibroblasts, airway epithelial cells, and endothelial cells—and then periostin contributes to generating thick basement membranes, a typical histological feature in asthma patients. Periostin would play a role in accelerating airway allergic inflammation in asthma by acting as a matricellular protein. Serum periostin has characteristics as a biomarker, reflecting both type 2 inflammation and remodeling/fibrosis in asthma patients. These characteristics are useful for stratifying asthma patients and can predict the ICS resistance or efficacy of molecularly targeted drugs such as IL-4/IL-13 antagonists for asthma patients.
KeywordsBiomarker Matricellular protein Molecularly targeted drug IL-4 IL-13
We thank Dr. Dovie R. Wylie for the critical review of this manuscript. We also thank the following colleagues and collaborators for contributing to the present work: Go Takayama, Masaru Uchida, Miho Masuoka, Hiroshi Shiraishi, Kanako Ontsuka, Kazuto Taniguchi, Yasutaka Mitamura, Tomohito Yoshihara, Kazuhiko Arima, Shoichi Suzuki, Shoichiro Ohta, Go Kato, Koichiro Takahashi, Shin-ichiro Hayashi (Saga Medical School), Noriko Yuyama (Genox Research, Inc.), Akihiro Ishida, Nobuo Ohta (Yamagata University), Hiroshi Fujishima (Tsurumi University), Naoko Okada, Kenji Matsumoto (National Research Institute for Child Health and Development Laboratory), Yoshihiro Kanemitsu, Tadao Nagasaki, Tomoko Tajiri, Hisako Matsumoto (Kyoto University), Masako Matsuzaka, Koichi Fukunaga (Keio University), Koichiro Asano (Tokai University), Yorihisa Kotobuki, Ichiro Katayama (Osaka University), Kenzen Kou, Yukie Yamaguchi, Michiko Aihara (Yokohama City University), Timothy Hinks, Peter Howarth (Southampton University Hospital), Mi-Ae Kim, Hae-Sim Park (Ajou University), Anna James, Sven-Erik Dahlen (Karolinska Institutet), Ayami Kamei, Yoshinori Azuma (Shino-Test Co.), Simon J. Conway (Indiana University), Masaki Okamoto, Tomoaki Hoshino, and Kiminori Fujimoto (Kurume University).
- 2.Horiuchi K, Amizuka N, Takeshita S, Takamatsu H, Katsuura M, Ozawa H, et al. Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor β. J Bone Miner Res. 1999;14:1239–49.CrossRefGoogle Scholar
- 44.Hanania NA, Korenblat P, Chapman KR, Bateman ED, Kopecky P, Paggiaro P, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2016;4:781–96.CrossRefGoogle Scholar
- 46.Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;376:1090–1.Google Scholar
- 47.Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388:31–44.CrossRefGoogle Scholar