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Research on modification of Mediterranean fever gene variants in autoimmune diseases

Research Project

Project/Area Number 19K17888
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionNagasaki 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
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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 / 関節リウマチ
Outline of Research at the Start

本研究では、家族性地中海熱の原因遺伝子であるMEFV遺伝子の本邦のパターンとして多いExon 2多型の病的意義や自己免疫疾患への影響を動物実験により解明を試み、また臨床研究としてSLE患者にMEFV遺伝子解析を実施することで、その変異/多型がSLEの臨床病態に与える影響を解明する。また本研究では、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おり、革新的な治療シーズを提供する可能性がある。

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.

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。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (22 results)

All 2023 2022 2021 2020 2019

All Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 9 results) Presentation (7 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] The immunoregulatory roles of non-haematopoietic cells in the kidney2023

    • Author(s)
      Tsokos George C.、Boulougoura Afroditi、Kasinath Vivek、Endo Yushiro、Abdi Reza、Li Hao
    • Journal Title

      Nature Reviews Nephrology

      Volume: 20 Issue: 4 Pages: 206-217

    • DOI

      10.1038/s41581-023-00786-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of calcium/calmodulin-dependent protein kinase IV in arthritis: dual effect on Th17 cell activation and osteoclastogenesis2023

    • Author(s)
      Tomohiro Koga, Masataka Umeda, Nobuya Yoshida, Yushiro Endo, Atsushi Kawakami, George C Tsokos
    • Journal Title

      Rheumatology (Oxford)

      Volume: 62 Issue: 2 Pages: 861-871

    • DOI

      10.1093/rheumatology/keac381

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Abnormalities of T cells in systemic lupus erythematosus: new insights in pathogenesis and therapeutic strategies2022

    • Author(s)
      Hao Li, Afroditi Boulougoura, Yushiro Endo, George C Tsokos
    • Journal Title

      J Autoimmun

      Volume: 132 Pages: 102870-102870

    • DOI

      10.1016/j.jaut.2022.102870

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autoinflammatory disease: clinical perspectives and therapeutic strategies2022

    • Author(s)
      Kawakami Atsushi、Endo Yushiro、Koga Tomohiro、Yoshiura Koh-ichiro、Migita Kiyoshi
    • Journal Title

      Inflammation and Regeneration

      Volume: 42 Issue: 1 Pages: 37-37

    • DOI

      10.1186/s41232-022-00217-7

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Large deletion in 6q containing the TNFAIP3 gene associated with autoimmune lymphoproliferative syndrome2022

    • Author(s)
      Endo Yushiro、Funakoshi Yasutomo、Koga Tomohiro、Ohashi Hirofumi、Takao Mami、Miura Kiyonori、Yoshiura Koh-ichiro、Matsumoto Tadashi、Moriuchi Hiroyuki、Kawakami Atsushi
    • Journal Title

      Clinical Immunology

      Volume: 235 Pages: 108853-108853

    • DOI

      10.1016/j.clim.2021.108853

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tocilizumab has no direct effect on cell lines infected with human T-cell leukemia virus type 1.2021

    • Author(s)
      Endo Y, Fukui S, Koga T, Sasaki D, Hasegawa H, Yanagihara K, Okayama A, Nakamura T, Kawakami A, Nakamura H. Tocilizumab has no direct effect on cell lines infected with human T-cell leukemia virus type 1.
    • Journal Title

      J Int Med Res.

      Volume: 49 Issue: 3 Pages: 1-10

    • DOI

      10.1177/03000605211002083

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discrepancy between clinical and ultrasound remissions in rheumatoid arthritis: a multicentre ultrasound cohort study in Japan2021

    • Author(s)
      Endo Y、Kawashiri S-Y、Nishino A、Okamoto M、Tsuji S、Shimizu T、Sumiyoshi R、Igawa T、Koga T、Iwamoto N、Ichinose K、Tamai M、Nakamura H、Origuchi T、Ueki Y、Yoshitama T、Eiraku N、Matsuoka N、Okada A、Fujikawa K、Otsubo H、Takaoka H、Hamada H、Tsuru T、Nagano S、Arinobu Y、Hidaka T、Tada Y、Kawakami A
    • Journal Title

      Scandinavian Journal of Rheumatology

      Volume: 50 Issue: 6 Pages: 436-441

    • DOI

      10.1080/03009742.2021.1876914

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis2021

    • Author(s)
      Endo Yushiro、Kawashiri Shin-ya、Morimoto Shimpei、Nishino Ayako、Okamoto Momoko、Tsuji Sosuke、Takatani Ayuko、Shimizu Toshimasa、Sumiyoshi Remi、Igawa Takashi、Koga Tomohiro、Iwamoto Naoki、
    • Journal Title

      Medicine

      Volume: 100 Issue: 1 Pages: e23254-e23254

    • DOI

      10.1097/md.0000000000023254

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systemic lupus erythematosus overlapping dermatomyositis owing to a heterozygous TREX1 Asp130Asn missense mutation2021

    • Author(s)
      Endo Yushiro、Koga Tomohiro、Otaki Hiroki、Furukawa Kaori、Kawakami Atsushi
    • Journal Title

      Clinical Immunology

      Volume: 227 Pages: 108732-108732

    • DOI

      10.1016/j.clim.2021.108732

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness and safety of non-tumor necrosis factor inhibitor therapy for anti-human T-cell leukemia virus type 1 antibody-positive rheumatoid arthritis2020

    • Author(s)
      Endo Yushiro、Fukui Shoichi、Umekita Kunihiko、Kawakami Atsushi、Nakamura Hideki、et al
    • Journal Title

      Modern Rheumatology

      Volume: - Issue: 5 Pages: 972-978

    • DOI

      10.1080/14397595.2020.1847802

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-citrullinated protein antibody titre as a predictor of abatacept treatment persistence in patients with rheumatoid arthritis: a prospective cohort study in Japan2020

    • Author(s)
      Endo Y, Koga T, Kawashiri S, Morimoto S, Nishino A, Umeda M, Fukui S, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Ueki Y, Yoshitama T, Eiraku N, Matsuoka N, Okada A, Fujikawa K, Hamada H, Tsuru T, Nagano S, Arinobu Y, Hidaka T, Tada Y, Kawakami A
    • Journal Title

      Scand J Rheumatol

      Volume: 49 Pages: 13-17

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful hydroxychloroquine treatment for familial Mediterranean fever in a Japanese patient with concurrent systemic lupus erythematosus2020

    • Author(s)
      Endo Y, Koga T, Furukawa K, Umeda M, Sasaki D, Yanagihara K, Kawakami A
    • Journal Title

      Rheumatology

      Volume: 59 Pages: 903-905

    • Related Report
      2019 Research-status Report
  • [Journal Article] Lung consolidation and mediastinal lymphadenopathy in patients with early anti-citrullinated protein antibody-positive rheumatoid arthritis.2019

    • Author(s)
      Endo Y, Koga T, Tsutsui S, Ashizawa K, Kawashiri S, Kawakami A
    • Journal Title

      Clinical and Experimental Rheumatology

      Volume: 37 Pages: 517-518

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Atypical phenotype without fever in a Japanese family with an autosomal dominant transmission of familial Mediterranean fever due to heterozygous MEFV Thr577Asn mutations2019

    • Author(s)
      Endo Y, Koga T, Nakashima M, Mishima H, Yoshiura K, Kawakami A
    • Journal Title

      Clinical and Experimental Rheumatology

      Volume: 37 Pages: 161-162

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Late-onset protracted febrile myalgia syndrome successfully treated with colchicine owing to heterozygous MEFV exon 2 variants2019

    • Author(s)
      Endo Y, Koga T, Furukawa K, Sumiyoshi R, Ichinose K, Kawakami A
    • Journal Title

      Clinical and Experimental Rheumatology

      Volume: 37 Pages: 166-166

    • Related Report
      2019 Research-status Report
  • [Presentation] Presence of Mediterranean Fever Gene Variants Provides Protection from the Development of Lupus Nephritis in Patients with Systemic Lupus Erythematosus2023

    • Author(s)
      Yushiro Endo, Tomohiro Koga, Atsushi Kawakami
    • Organizer
      American College of Rheumatology Convergence 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗HTLV-1抗体陽性関節リウマチにおける 非TNF阻害薬の臨床効果と安全性2020

    • Author(s)
      遠藤 友志郎、中村 英樹、梅北 邦彦、岡田 覚丈、藤川 敬太、荒牧 俊幸、松岡 直樹、植木 幸孝、日髙 利彦、岡山 昭彦、川上 純
    • Organizer
      第117回日本内科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Consolidations in the lung and mediastinal lymphadenopathy occur predominantly in early anti-citrullinated protein antibody-positive patients with rheumatoid arthritis2019

    • Author(s)
      遠藤友志郎、古賀智裕、筒井伸、芦澤和人、江口瑞奈、岡本百々子、辻創介、高谷亜由子、清水俊匡、住吉玲美、井川敬、川尻真也、岩本直樹、一瀬邦弘、玉井慎美、中村英樹、折口智樹、川上純
    • Organizer
      アジア太平洋リウマチ学会2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Lung consolidation and mediastinal lymphadenopathy in patients with early anti-citrullinated protein antibody-positive rheumatoid arthritis2019

    • Author(s)
      遠藤友志郎、古賀智裕、筒井伸、芦澤和人、江口瑞奈、岡本百々子、辻創介、高谷亜由子、清水俊匡、住吉玲美、井川敬、川尻真也、岩本直樹、一瀬邦弘、玉井慎美、中村英樹、折口智樹、川上純
    • Organizer
      第63回 日本リウマチ学会総会・学術集会 国際ワークショップ
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗HTLV-1抗体陽性関節リウマチにおける非TNF阻害薬の臨床効果2019

    • Author(s)
      遠藤友志郎、中村英樹、梅北邦彦、宮本潤哉、岡田覚丈、古賀智裕、藤川敬太、荒牧俊幸、溝上明成、松岡直樹、植木幸孝、仮屋裕美、橋場弥生、日髙利彦、岡山昭彦、川上純
    • Organizer
      第6回 日本HTLV-1学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Positivity of Anti-Ro/SSA Antibody Confer Poor Response and Persistence with Abatacept Therapy2019

    • Author(s)
      遠藤友志郎、古賀智裕、川尻真也、西野文子、岩本直樹、一瀬邦弘、玉井慎美、中村英樹、折口智樹、吉玉珠美、榮樂信隆、植木幸孝、松岡直樹、岡田覚丈、都留智己、日髙利彦、藤川敬太、濱田浩朗、永野修司、有信洋二郎、多田芳文、川上純
    • Organizer
      アメリカリウマチ学会2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Efficacy and Safety of Tocilizumab Treatment for Anti-human T Lymphotropic Virus Type I Antibody-positive Rheumatoid Arthritis2019

    • Author(s)
      遠藤友志郎、中村英樹、梅北邦彦、福井翔一、鈴木貴久、宮本潤哉、岡田覚丈、古賀智裕、藤川敬太、荒牧俊幸、溝上明成、松岡直樹、植木幸孝、仮屋裕美、橋場弥生、日髙利彦、岡山昭彦、川上純
    • Organizer
      アメリカリウマチ学会2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2025-01-30  

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