カトウ　タマキ   Katou Tamaki   加藤　環    所属   医学部 医学科（東京女子医科大学病院）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase δ syndrome-like immunodeficiency.
掲載誌名	正式名：The Journal of allergy and clinical immunology 略　 称：J Allergy Clin Immunol ISSNコード：10976825/00916749
掲載区分	国外
巻・号・頁	138(6),pp.1672-1680.e10
著者・共著者	Tsujita Yuki, Mitsui-Sekinaka Kanako, Imai Kohsuke, Yeh Tzu-Wen, Mitsuiki Noriko, Asano Takaki, Ohnishi Hidenori, Kato Zenichiro, Sekinaka Yujin, Zaha Kiyotaka, Kato Tamaki, Okano Tsubasa, Takashima Takehiro, Kobayashi Kaoru, Kimura Mitsuaki, Kunitsu Tomoaki, Maruo Yoshihiro, Kanegane Hirokazu, Takagi Masatoshi, Yoshida Kenichi, Okuno Yusuke, Muramatsu Hideki, Shiraishi Yuichi, Chiba Kenichi, Tanaka Hiroko, Miyano Satoru, Kojima Seiji, Ogawa Seishi, Ohara Osamu, Okada Satoshi, Kobayashi Masao, Morio Tomohiro, Nonoyama Shigeaki
発行年月	2016/12
概要	BACKGROUND:Activated phosphatidylinositol 3-kinase δ syndrome (APDS) is a recently discovered primary immunodeficiency disease (PID). Excess phosphatidylinositol 3-kinase (PI3K) activity linked to mutations in 2 PI3K genes, PIK3CD and PIK3R1, causes APDS through hyperphosphorylation of AKT, mammalian target of rapamycin (mTOR), and S6.OBJECTIVE:This study aimed to identify novel genes responsible for APDS.METHODS:Whole-exome sequencing was performed in Japanese patients with PIDs. Immunophenotype was assessed through flow cytometry. Hyperphosphorylation of AKT, mTOR, and S6 in lymphocytes was examined through immunoblotting, flow cytometry, and multiplex assays.RESULTS:We identified heterozygous mutations of phosphatase and tensin homolog (PTEN) in patients with PIDs. Immunoblotting and quantitative PCR analyses indicated that PTEN expression was decreased in these patients. Patients with PTEN mutations and those with PIK3CD mutations, including a novel E525A mutation, were further analyzed. The clinical symptoms and immunologic defects of patients with PTEN mutations, including lymphocytic AKT, mTOR, and S6 hyperphosphorylation, resemble those of patients with APDS. Because PTEN is known to suppress the PI3K pathway, it is likely that defective PTEN results in activation of the PI3K pathway.CONCLUSION:PTEN loss-of-function mutations can cause APDS-like immunodeficiency because of aberrant PI3K pathway activation in lymphocytes.
DOI	10.1016/j.jaci.2016.03.055
PMID	27426521