Elucidation of molecular mechanism of cytopenia associated with immunodeficiency/immune disorder

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293244
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Morio Tomohiro 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (30239628)
• Co-Investigator(Kenkyū-buntansha): 小原 收 公益財団法人かずさDNA研究所, 技術開発研究部, 副所長・部長 (20370926)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 遺伝子 / 免疫学 / 臨床

Outline of Final Research Achievements

We hypothesized that cytopenia in common variable immunodeficiency (CVID) could be due to 1) autoantibody, 2) hemophagocytosis, 3) differentiation blockade, and 4) increased cell death of a particular lineage. We looked at the involvement of each machinery in different CVID patients and elucidated the following. 1) IgH repertoire was skewed and the size of SHM was reduced in activated PI3Kδ syndrome. 2) IFN-g production was augmented in some of STAT1-GOF-CMCD patients. 3) Common lymphoid precursors were reduced in newly identified B cell deficiency due to heterologous mutation of IKZF1. 4) T cells were activated and induced to cell death in TNFAIP3 (A20) deficiency. Through whole exome analysis on samples from CVID patients with cytopenia, we have identified two novel genes and have carried out functional analysis using model cell systems.

Free Research Field

小児科学、免疫学