Persistent Impairment of T-Cell Regeneration in a Patient with Activated PI3K δ Syndrome
- 317 Downloads
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...
KeywordsRapamycin Hematopoietic Stem Cell Transplantation Rapamycin Treatment Quantitative Polymerase Chain Reaction Analysis mTOR Inhibitor Rapamycin
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
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 was obtained from all individual participants included in the study.
Conflict of Interest
The authors declare that they have no conflict of interest.