Examination of the role of the new inflammation unit Pyrin inframasome in chronic inflammatory diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08899
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Kurume University
• Principal Investigator: IDA Hiroaki 久留米大学, 医学部, 教授 (60363496)
• Co-Investigator(Kenkyū-buntansha): 海江田 信二郎 久留米大学, 医学部, 准教授 (20330798) ; 山崎 聡士 久留米大学, その他部局等, 准教授 (30367388)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Pyrinインフラマソーム / MEFV / S242R / E148Q

Outline of Final Research Achievements

We analyzed the activation mechanism of the Pyrin inflammasome, which is important for the pathophysiology of familial Mediterranean fever (FMF), and the significance of the MEFV exon 2 variant E148Q, which is especially common in Japan. First, we established the iPS cells derived from the first PAAND (pyrin-associated autoinflammation with neutrophic dermatosis) patient in Japan and were able to differentiate into neutrophils, but we could not secure a sufficient number. In the clinical picture of patients with fever of unknown origin and analysis of gene variants, the compound heterozygotes group containing the E148Q variant had a significantly higher FMF diagnosis rate than the E148Q variant heterozygotes group. It was suggested that the E148Q variant acts as a modifier of other risk alleles by adding other MEFV variants to the E148Q variant, lowers the threshold for disease susceptibility, and contributes to the onset of FMF.

Free Research Field

自己炎症性疾患

Academic Significance and Societal Importance of the Research Achievements

本邦初のPAAND患者由来のiPS細胞を樹立(細胞バンク登録)できたことは、今後のPyrinインフラマソーム解析に役立つツールとなると考えられる。本邦に多いMEFVエクソン2変異の解釈として、E148Q変異が疾患感受性に対する閾値を低下させ、FMF発症に寄与する可能性が示唆されたことは、学術的にも意義がある。本邦で臨床的にも変異の解釈で問題となっているE148Q変異への考え方に一石を投じたと思われる。