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2 results on '"Takaki Asano"'

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

Author

Osamu Ohara, Kohsuke Imai, Taizo Wada, Kunio Hashimoto, Akira Shimada, Kanako Mitsui-Sekinaka, Tzu-Wen Yeh, Takaki Asano, and Youjiro Ichinose

Subjects
Flow Cytometry, immunodeficiency, Akt phosphorylation, Activated PI3 kinase delta syndrome, catalytic subunit p110δ of phosphatidylinositol 3-kinase, regulatory subunit p85α of phosphatidylinositol 3-kinase, Immunologic diseases. Allergy, RC581-607
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 to CD10- mature B cells. Enhanced pAKT was not observed in B cells of healthy controls, patients with common variable immunodeficiency (CVID), and hyper IgM syndrome (HIGM) 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.

Published
2018
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2. Enhanced AKT Phosphorylation of Circulating B Cells in Patients With Activated PI3Kδ Syndrome

Author

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

Subjects
lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Adult, Male, Hyper IgM syndrome, AKT phosphorylation, catalytic subunit p110δ of phosphatidylinositol 3-kinase, Adolescent, Class I Phosphatidylinositol 3-Kinases, CD14, Immunology, CD19, 03 medical and health sciences, Phosphatidylinositol 3-Kinases, Young Adult, medicine, Immunology and Allergy, Humans, Amino Acid Sequence, Phosphorylation, Protein kinase B, PI3K/AKT/mTOR pathway, Original Research, B-Lymphocytes, regulatory subunit p85α of phosphatidylinositol 3-kinase, CD40, biology, Chemistry, Common variable immunodeficiency, Precursor Cells, B-Lymphoid, flow cytometry, Immunologic Deficiency Syndromes, medicine.disease, Pedigree, Class Ia Phosphatidylinositol 3-Kinase, 030104 developmental biology, activated PI3 kinase delta syndrome, P110δ, Mutation, Cancer research, biology.protein, Female, lcsh:RC581-607, Proto-Oncogene Proteins c-akt, immunodeficiency
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., 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.

Published
2018

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