Studies on Immune Disease
Clinical and immunological analysis of patients with activated phosphoinositide 3-kinase δ syndrome resulting from PIK3CD mutation
Tang Wenjing, Wang Wei, Luo Ying, Wang Yanping, Li Li, An Yunfei, Gou Lijuan, Ma Mingsheng, He Tingyan, Yang Jun, Zhao Xiaodong, Song Hongmei
Published 2017-01-02
Cite as Chin J Pediatr, 2017, 55(1): 19-24. DOI: 10.3760/cma.j.issn.0578-1310.2017.01.004
Abstract
ObjectiveTo explore the clinical and immunological features, gene mutations, treatment and prognosis in patients with activated phosphoinositide 3-kinase δ syndrome (APDS) caused by PIK3CD gene heterozygous germline mutation.
MethodThe data of clinical, immunological phenotype, treatment, and prognosis of 15 patients with APDS, who visited Children′s Hospital of Chongqing Medical University, Peking Union Medical College Hospital, and Shenzhen Children′s Hospital from June 2014 to November 2016, were collected and analyzed.
ResultOf the 15 patients, 11 were males, remaining 4 patients were females. The median age of disease onset was 1 year, and median age at diagnosis was 4 years and 4 months. All patients had the de novo heterozygous germline mutation in PIK3CD (c. 3061G>A, p. E1021K). The common initial symptoms were respiratory infections, including pneumonia (12 cases) , bronchiectasis (5 cases). Other common clinical manifestations were recurrent and chronic diarrhea (11 cases), Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV) viremia (10 cases), hepatosplenomegaly (13 cases), and lymphadenopathy (10 cases). The main immunological features were increased IgM (11 cases), decreased IgG (6 cases), decreased numbers of CD4+ T cell (7 cases) especially naïve CD4+ T cell (9 cases), reduced numbers of B cells (11 cases) particularly naïve B cells (9 cases), increased numbers of transitional B cells (5 cases) and CD8+ terminally differentiated effector memory T cells (5 cases). After 1-29 months follow up, 13 of the 15 cases remain survived, of whom 5 cases received regular intravenous immunoglobulin (IVIG) therapy, with reduced frequency of infections and improved severity of infections; of whom 3 cases received oral rapamycin therapy at the dosage of 1 mg/ (m2·d) and with a decrease in nonneoplastic lymphoproliferation.
ConclusionE1021K is a hotspot for mutation in the PIK3CD gene in patients with APDS. Regular IVIG can improve their quality of life. Targetel treatment with rapamycin could mitigate hepatosplenomegaly.
Key words:
Respiratory tract infections; Genes, PIK3CD; Primary immunodeficiency diseases
Contributor Information
Tang Wenjing
Department of Rheumatology and Immunology, Children′s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing 400014, China
Wang Wei
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Luo Ying
Department of Nephrology and Immunology, Shenzhen Children′s Hospital, Shenzhen 518038, China
Wang Yanping
Li Li
An Yunfei
Gou Lijuan
Ma Mingsheng
He Tingyan
Yang Jun
Zhao Xiaodong
Song Hongmei
