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

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

Frontiers in Immunology

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.

activated PI3 kinase delta syndrome

AKT phosphorylation

catalytic subunit p110δ of phosphatidylinositol 3-kinase

flow cytometry

immunodeficiency

regulatory subunit p85α of phosphatidylinositol 3-kinase

Medical sciences [ 490 ]

eng

Frontiers Media S.A.

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.

[ISSN] 1664-3224

[DOI] 10.3389/fimmu.2018.00568

[PMID] 29675019