Elucidation of human immunoglobulin class switch recombination mechanism by the identification of causative gene for hyper-IgM syndrome

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09640
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: IMAI Kohsuke 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (90332626)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 原発性免疫不全症 / 免疫グロブリンクラススイッチ / 抗体産生不全症

Outline of Final Research Achievements

Whole exome sequencing of primary antibody deficiency including hyper- IgM syndrome (HIGM) type 4 revealed the mutations in 20 genes. Twenty-two patients with activated PI3Kδ syndrome (APDS) type 1 were identified from the low-TREC group. Increased transitional B cells / follicular T cells / plasmablasts and decreased CD4 helper T cells were useful for diagnosis. Long-term event-free survival was poor, but hematopoietic stem cell transplantation was effective. Low serum IgG2 was observed in 90%, and IgG2 class switch recombination was impaired in vitro. How activated PI3Kδ inhibits IgG2 class switch will be analyzed in the future.

Free Research Field

原発性免疫不全症