Research on modification of Mediterranean fever gene variants in autoimmune diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17888
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Nagasaki University
• Principal Investigator: Endo Yushiro 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (10831571)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 家族性地中海熱 / 遺伝性自己炎症性疾患 / 全身性エリテマトーデス / 自己免疫疾患

Outline of Final Research Achievements

We reviewed the case of Japanese patients with SLE. Also, we partially introduced human exon 2 of the MEFV gene with or without E148Q variant into those in MRL/lpr mice (MRL/lpr hMEFV WT vs MRL/lpr hMEFV E148Q). Patients with MEFV variants exhibited significant lower presence of lupus nephritis than those without MEFV variants. We counted the total number of MEFV variants exhibited in each patient. The total number of MEFV variants in patients with lupus nephritis was significantly lower than those lacking lupus nephritis. Consistent with the data from patients with SLE, MRL/lpr hMEFV E148Q showed the tendency of less severity in lupus nephritis (Not significant) and showed significantly less autoantibody production. The differences in those phenotypes was suggested to be attributed by less induction of dendritic cells followed by less memory B cells. Our results suggested that presence of MEFV variants provides protection from the development of lupus nephritis in patients with SLE.

Free Research Field

自己免疫・自己炎症性疾患

Academic Significance and Societal Importance of the Research Achievements

SLEを含めた自己免疫疾患は、T細胞やB細胞のみならず、自然免疫担当細胞の関与も注目されているが、これまで自己免疫疾患のモデルマウスを用いたMEFV遺伝子の機能的解析を行った先行研究はなく学術的な独自性が高く、今回の研究では自己炎症性疾患と自己免疫疾患という別カテゴリーの疾患が互いの病態に与える影響やその機序を解くことで、その他の自己炎症性疾患や自己免疫疾患についても更なる理解や研究が進むきっかけになることが期待される点で学術的意義が高く、自己炎症性疾患に関連する遺伝子に注目することで、自己免疫疾患の病態解明につながる可能性を秘めている点において社会的意義も高い。