Genetic basis and molecular mechanism of anti-NMDAR encephalitis in early infant.

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15716
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Hiroshima University
• Principal Investigator: Kobayashi Yoshiyuki 広島大学, 病院(医), 助教 (20723290)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 抗NMDAR脳炎 / 若年発症 / IRAK4欠損症

Outline of Final Research Achievements

IRAK4 deficiency is an immunodeficiency syndrome caused by impairment of innate immunity, and early diagnosis is extremely important to prevent severe and fetal outcomes. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, on the other hand, is an autoimmune encephalitis characterized by central hypoventilation and involuntary movements. Since infantile-onset anti-NMDAR encephalitis is very rare, we performed whole exome analysis and identified novel heterozygous mutations in IRAK4 (Y10Cfs*9, R12P). We performed functional analysis of both mutations and established a novel evaluation system to properly assess IRAK4 mutations. In this study, we also suggest the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

抗NMDAR脳炎を発症したIRAK4欠損症の症例を世界で初めて同定し、稀少疾患に着目したという点で、独自性が高い。また、IRAK4欠損HEK293T細胞を用いることでIRAK4遺伝子変異の病的意義を簡便かつ正確に評価できる新規のNF-kBレポーターアッセイを確立した部分で学術的意義や社会的意義は高い。同時に乳児期発症の抗NMDAR脳炎が先天的な免疫異常に基づいて発症する可能性を示唆した部分でも学術的意義は高いと考える。