Journal of Clinical Immunology

, Volume 37, Issue 4, pp 347–350 | Cite as

Persistent Impairment of T-Cell Regeneration in a Patient with Activated PI3K δ Syndrome

  • Fumihiro Goto
  • Toru UchiyamaEmail author
  • Yumiko Nakazawa
  • Kohsuke Imai
  • Toshinao Kawai
  • Masafumi Onodera
Letter to Editor

To the Editor:

It was recently reported that gain-of-function mutations in PIK3CD, which encodes the p110δ catalytic subunit of PI3K, causes activated PI3K δ syndrome (APDS). Constitutive activation of the PI3K-Akt-mTOR pathway facilitates the proliferation and senescence of effector CD8+T cells and a defect of naïve T cells [1, 2]. Patients also show an abnormal B-cell differentiation with an increased number of transitional B cells and decreased number of class-switched B cells, resulting in a low serum level of class-switched immunoglobulin. Therefore, patients suffering from APDS experience recurrent respiratory infection and chronic viremia due to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections. Hepatosplenomegaly and lymphadenopathy reflect an additional characteristic state of uncontrollable lymphoproliferation in APDS. These immunologic characteristics can be explained by the increased phosphorylation of Akt and constitutive activation of mechanistic target of...


Rapamycin Hematopoietic Stem Cell Transplantation Rapamycin Treatment Quantitative Polymerase Chain Reaction Analysis mTOR Inhibitor Rapamycin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The manuscript was proofread and edited by Dr. Julian Tang of the Department of Education for Clinical Research, National Center for Child Health and Development (NCCHD). We would like to thank the patient and family for their cooperation. We are also grateful to Nobuyuki Watanabe and other laboratory staff at the Department of Human Genetics, NCCHD for their excellent support. This work was supported by grants from the Japan Agency for Medical Research and Development, Japan (Grant number: 15gk0110005h0103), and the NCCHD (Grant number: 25-1) (Masafumi Onodera).

Compliance with Ethical Standards

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amenders or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10875_2017_393_MOESM1_ESM.pptx (1.3 mb)
Fig. S1 (PPTX 1376 kb)
10875_2017_393_MOESM2_ESM.docx (104 kb)
Table S1 (DOCX 103 kb)


  1. 1.
    Angulo I, Vadas O, Garcon F, Banham-Hall E, Plagnol V, et al. Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342(6160):866–71.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15(1):88–97.CrossRefPubMedGoogle Scholar
  3. 3.
    Rae W, Ramakrishnan KA, Gao Y, Ashton-Key M, Pengelly RJ, et al. Precision treatment with sirolimus in a case of activated phosphoinositide 3-kinase delta syndrome. Clin Immunol. 2016;171:38–40.CrossRefPubMedGoogle Scholar
  4. 4.
    Chapman NM, Chi HB. mTOR links environmental signals to T cell fate decisions. Front Immunol. 2015;5:1–11.CrossRefGoogle Scholar
  5. 5.
    Kerdiles YM, Beisner DR, Tinoco R, Dejean AS, Castrillon DH, et al. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat Immunol. 2009;10(2):176–84.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Human GeneticsNational Center for Child Health and DevelopmentTokyoJapan
  2. 2.Department of Community Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan

Personalised recommendations