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

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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

Keywords

  • AKT phosphorylation
  • Activated PI3 kinase delta syndrome
  • 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

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    Asano, T., Okada, S., Tsumura, M., Yeh, T. W., 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, 9(APR), [568]. https://doi.org/10.3389/fimmu.2018.00568