Enhanced AKT phosphorylation of circulating B cells in patients with activated PI3Kδ syndrome

Takaki Asano, Satoshi Okada, Miyuki Tsumura, Tzu Wen Yeh, Kanako Mitsui-Sekinaka, Yuki Tsujita, Youjiro Ichinose, Akira Shimada, Kunio Hashimoto, Taizo Wada, Kohsuke Imai, Osamu Ohara, Tomohiro Morio, Shigeaki Nonoyama, Masao Kobayashi

Research output: Contribution to journal › Article

3 Citations (Scopus)

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.

Original languageEnglish
Article number568
JournalFrontiers in Immunology
Volume9
Issue numberAPR
DOIs
Publication statusPublished - Apr 5 2018

Fingerprint

1-Phosphatidylinositol 4-Kinase
B-Lymphocytes
Phosphorylation
Monocytes
Hyper-IgM Immunodeficiency Syndrome
Common Variable Immunodeficiency
CD40 Ligand
B-Lymphoid Precursor Cells
Respiratory Tract Infections
Flow Cytometry
Immunoglobulin G
Lymphocytes
T-Lymphocytes
Mutation
Antibodies

Keywords

  • Activated PI3 kinase delta syndrome
  • AKT phosphorylation
  • Catalytic subunit p110δ of phosphatidylinositol 3-kinase
  • Flow cytometry
  • Immunodeficiency
  • Regulatory subunit p85a of phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Asano, T., Okada, S., Tsumura, M., Yeh, T. W., Mitsui-Sekinaka, K., Tsujita, Y., ... Kobayashi, M. (2018). Enhanced AKT phosphorylation of circulating B cells in patients with activated PI3Kδ syndrome. Frontiers in Immunology, 9(APR), [568]. https://doi.org/10.3389/fimmu.2018.00568

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.

In: Frontiers in Immunology, Vol. 9, No. APR, 568, 05.04.2018.

Research output: Contribution to journal › Article

Asano, T, Okada, S, Tsumura, M, Yeh, TW, Mitsui-Sekinaka, K, Tsujita, Y, Ichinose, Y, Shimada, A, Hashimoto, K, Wada, T, Imai, K, Ohara, O, Morio, T, Nonoyama, S & Kobayashi, M 2018, 'Enhanced AKT phosphorylation of circulating B cells in patients with activated PI3Kδ syndrome', Frontiers in Immunology, vol. 9, no. APR, 568. https://doi.org/10.3389/fimmu.2018.00568
Asano T, Okada S, Tsumura M, Yeh TW, Mitsui-Sekinaka K, Tsujita Y et al. Enhanced AKT phosphorylation of circulating B cells in patients with activated PI3Kδ syndrome. Frontiers in Immunology. 2018 Apr 5;9(APR). 568. https://doi.org/10.3389/fimmu.2018.00568
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. / Enhanced AKT phosphorylation of circulating B cells in patients with activated PI3Kδ syndrome. In: Frontiers in Immunology. 2018 ; Vol. 9, No. APR.
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AU - Asano, Takaki

AU - Okada, Satoshi

AU - Tsumura, Miyuki

AU - Yeh, Tzu Wen

AU - Mitsui-Sekinaka, Kanako

AU - Tsujita, Yuki

AU - Ichinose, Youjiro

AU - Shimada, Akira

AU - Hashimoto, Kunio

AU - Wada, Taizo

AU - Imai, Kohsuke

AU - Ohara, Osamu

AU - Morio, Tomohiro

AU - Nonoyama, Shigeaki

AU - Kobayashi, Masao

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AB - 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.

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