TY - JOUR
T1 - Enhanced AKT phosphorylation of circulating B cells in patients with activated PI3Kδ syndrome
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
N1 - Funding Information:
We thank Michael Ciancanelli for proofreading. 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
Publisher Copyright:
© 2018 Asano, Okada, Tsumura, Yeh, Mitsui-Sekinaka, Tsujita, Ichinose, Shimada, Hashimoto, Wada, Imai, Ohara, Morio, Nonoyama and Kobayashi.
PY - 2018/4/5
Y1 - 2018/4/5
N2 - 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.
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.
KW - AKT phosphorylation
KW - Activated PI3 kinase delta syndrome
KW - Catalytic subunit p110δ of phosphatidylinositol 3-kinase
KW - Flow cytometry
KW - Immunodeficiency
KW - Regulatory subunit p85a of phosphatidylinositol 3-kinase
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U2 - 10.3389/fimmu.2018.00568
DO - 10.3389/fimmu.2018.00568
M3 - Article
AN - SCOPUS:85045038400
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - APR
M1 - 568
ER -