PMID- 30499059 OWN - NLM STAT- MEDLINE DCOM- 20190930 LR - 20220801 IS - 1573-2592 (Electronic) IS - 0271-9142 (Linking) VI - 38 IP - 8 DP - 2018 Nov TI - Report of a Chinese Cohort with Activated Phosphoinositide 3-Kinase delta Syndrome. PG - 854-863 LID - 10.1007/s10875-018-0568-x [doi] AB - PURPOSE: We aimed to report the clinical manifestations and immunological features of activated phosphatidylinositol 3-kinase delta syndrome 1 (APDS1) in a Chinese cohort. Moreover, we investigated the efficacy and safety of rapamycin therapy for Chinese patients with APDS1. METHODS: Fifteen Chinese patients with APDS1 from 14 unrelated families were enrolled in this study. These patients were diagnosed based on clinical features, immunological phenotype, and whole-exome sequencing. Four patients were treated with rapamycin, and the clinical efficacy and safety of rapamycin were observed. The changes of phosphorylation of Akt and mammalian target of rapamycin (mTOR) signaling pathway after rapamycin treatment were detected by flow cytometry and real-time PCR. RESULTS: The common clinical manifestations of the patients included lymphadenopathy (93%), recurrent sinopulmonary infections (93%), hepatosplenomegaly (93%), and diarrhea (78%). Epstein-Barr virus (EBV) (80%) and fungus (Aspergillus) (47%) were the most common pathogens. Immunological phenotype included elevated Immunoglobulin (Ig) M levels (100%), decreased naive T cells, increased senescent T cells, and expanded transitional B cells. Whole-exome sequencing indicated that 13 patients had heterogeneous PIK3CD E1021K mutations, 1 patient had heterogeneous E1025G mutation and 1 patient had heterogeneous Y524N mutation. Gain-of-function (GOF) PIK3CD mutations increased the phosphorylation of the Akt-mTOR signaling pathway. Four patients underwent rapamycin therapy, experiencing substantial improvement in clinical symptoms and immunological phenotype. Rapamycin inhibited the activated Akt-mTOR signaling pathway. CONCLUSIONS: We described 15 Chinese patients with APDS1. Treatment with the mTOR inhibitor rapamycin improved patient outcomes. FAU - Wang, Ying AU - Wang Y AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Wang, Wenjie AU - Wang W AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Liu, Luyao AU - Liu L AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Hou, Jia AU - Hou J AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Ying, Wenjing AU - Ying W AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Hui, Xiaoying AU - Hui X AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Zhou, Qinhua AU - Zhou Q AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Liu, Danru AU - Liu D AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Yao, Haili AU - Yao H AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. FAU - Sun, Jinqiao AU - Sun J AUID- ORCID: 0000-0001-9125-8581 AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. jinqiaosun@fudan.edu.cn. FAU - Wang, Xiaochuan AU - Wang X AD - Department of Clinical Immunology, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. xchwang@shmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181129 PL - Netherlands TA - J Clin Immunol JT - Journal of clinical immunology JID - 8102137 RN - 0 (Immunoglobulin M) RN - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) RN - EC 2.7.1.137 (Class Ia Phosphatidylinositol 3-Kinase) RN - EC 2.7.1.137 (PIK3CD protein, human) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) RN - Activated PI3K-delta Syndrome SB - IM MH - Adolescent MH - Child MH - Child, Preschool MH - Class I Phosphatidylinositol 3-Kinases/genetics/immunology MH - Class Ia Phosphatidylinositol 3-Kinase/*metabolism MH - Cohort Studies MH - Female MH - Hepatomegaly MH - Humans MH - Immunoglobulin M/blood MH - Immunologic Deficiency Syndromes/drug therapy/*immunology MH - Infant MH - Lymphadenopathy MH - Male MH - Mutation/genetics MH - Oncogene Protein v-akt/metabolism MH - Phosphorylation MH - Precursor Cells, B-Lymphoid/*immunology MH - Primary Immunodeficiency Diseases MH - Respiratory Tract Infections MH - Signal Transduction MH - Sirolimus/*therapeutic use MH - T-Lymphocytes/*immunology MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - Activated phosphoinositide 3-kinase delta syndrome OT - PIK3CD gene OT - primary immunodeficiency OT - rapamycin EDAT- 2018/12/01 06:00 MHDA- 2019/10/01 06:00 CRDT- 2018/12/01 06:00 PHST- 2018/08/21 00:00 [received] PHST- 2018/11/06 00:00 [accepted] PHST- 2018/12/01 06:00 [pubmed] PHST- 2019/10/01 06:00 [medline] PHST- 2018/12/01 06:00 [entrez] AID - 10.1007/s10875-018-0568-x [pii] AID - 10.1007/s10875-018-0568-x [doi] PST - ppublish SO - J Clin Immunol. 2018 Nov;38(8):854-863. doi: 10.1007/s10875-018-0568-x. Epub 2018 Nov 29.