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ID 45835
file
creator
Asano, Takaki
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
subject
activated PI3 kinase delta syndrome
AKT phosphorylation
catalytic subunit p110δ of phosphatidylinositol 3-kinase
flow cytometry
immunodeficiency
regulatory subunit p85α of phosphatidylinositol 3-kinase
NDC
Medical sciences
abstract
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.
description
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.
journal title
Frontiers in Immunology
volume
Volume 9
start page
568
date of issued
2018-04-05
publisher
Frontiers Media S.A.
issn
1664-3224
publisher doi
pubmed id
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
publisher
rights
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.
department
Graduate School of Biomedical & Health Sciences
University Medical Hospital