Enhanced AKT Phosphorylation of Circulating B Cells in Patients With Activated PI3Kδ Syndrome

Frontiers in Immunology 9 巻 568- 頁 2018-04-05 発行

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タイトル ( eng )	Enhanced AKT Phosphorylation of Circulating B Cells in Patients With Activated PI3Kδ Syndrome
作成者	Asano Takaki Okada Satoshi Tsumura Miyuki Yeh Tzu-Wen Mitsui-Sekinaka Kanako Tsujita Yuki Ichinose Youjiro Shimada Akira Hashimoto Kunio Wada Taizo Imai Kohsuke Ohara Osamu Morio Tomohiro Nonoyama Shigeaki Kobayashi Masao
収録物名	Frontiers in Immunology
巻	9
開始ページ	568
抄録	Activated PI3Kδ syndrome (APDS) is a primary immunodeficiency characterized by recurrent respiratory tract infections, lymphoproliferation, and defective IgG production. Heterozygous mutations in PIK3CD, PIK3R1, or PTEN, which are related to the hyperactive phosphoinositide 3-kinase (PI3K) signaling, were recently presented to cause APDS1 or APDS2 (APDSs), or APDS-like (APDS-L) disorder. In this study, we examined the AKT phosphorylation of peripheral blood lymphocytes and monocytes in patients with APDSs and APDS-L by using flow cytometry. CD19+ B cells of peripheral blood in APDS2 patients showed the enhanced phosphorylation of AKT at Ser473 (pAKT) without any specific stimulation. The enhanced pAKT in CD19+ B cells was normalized by the addition of a p110δ inhibitor. In contrast, CD3+ T cells and CD14+ monocytes did not show the enhanced pAKT in the absence of stimulation. These findings were similarly observed in patients with APDS1 and APDS-L. Among CD19+ B cells, enhanced pAKT was prominently detected in CD10+ immature B cells compared with CD10− mature B cells. Enhanced pAKT was not observed in B cells of healthy controls, patients with common variable immunodeficiency, and hyper IgM syndrome due to CD40L deficiency. These results suggest that the enhanced pAKT in circulating B cells may be useful for the discrimination of APDS1, APDS2, and APDS-L from other antibody deficiencies.
著者キーワード	activated PI3 kinase delta syndrome AKT phosphorylation catalytic subunit p110δ of phosphatidylinositol 3-kinase flow cytometry immunodeficiency regulatory subunit p85α of phosphatidylinositol 3-kinase
内容記述	The Supplementary Material for this article can be found online at https://www.frontiersin.org/articles/10.3389/fimmu.2018.00568/full#supplementary-material. This study was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (16H05355 and 16K15528 to SO, 17H04233 to SN), the Ministry of Health, Labour and Welfare, Japan (17933299 to SN), and Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development, AMED.
NDC分類	医学 [ 490 ]
言語	英語
資源タイプ	学術雑誌論文
出版者	Frontiers Media S.A.
発行日	2018-04-05
権利情報	Copyright (c) 2018 Asano, Okada, Tsumura, Yeh, Mitsui-Sekinaka, Tsujita, Ichinose, Shimada, Hashimoto, Wada, Imai, Ohara, Morio, Nonoyama and Kobayashi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
出版タイプ	Version of Record（出版社版。早期公開を含む）
アクセス権	オープンアクセス
収録物識別子	[ISSN] 1664-3224 [DOI] 10.3389/fimmu.2018.00568 [PMID] 29675019