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Study of pathological condition of DIHS focusing on virus-derived microRNA and development of new diagnostic method

Research Project

Project/Area Number 17K10250
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionNara Medical University

Principal Investigator

ASADA HIDEO  奈良県立医科大学, 医学部, 教授 (60252681)

Co-Investigator(Kenkyū-buntansha) 宮川 史  奈良県立医科大学, 医学部, 講師 (00346024)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords薬剤性過敏症症候群 / DIHS / ヒトヘルペスウイルス / HHV-6 / 再活性化 / 持続感染 / microRNA / 薬疹 / βヘルペスウイルス
Outline of Final Research Achievements

Involvement of HHV-6 in the pathogenesis of DIHS has been suggested, but much remains unknown. Recently, it has been suggested that herpesvirus-derived microRNAs (miRNAs) are involved in the maintenance of latent infection and reactivation of herpesviruses. Therefore, we aimed to elucidate the pathogenesis of DIHS by identifying and analyzing HHV-6-derived miRNAs expressed in DIHS. We found that hhv6b-miR-Ro6-2 and -3, which are encoded in antisense of HHV-6 immediate early gene, were detected in serum and mononuclear cells during the acute phase of DIHS, and their expression was significantly correlated with clinical symptoms, suggesting that at least some HHV-6-derived miRNAs may be intimately involved in the pathogenesis of DIHS.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、HHV-6由来miRNAの1つであるhhv6b-miR-Ro6-2の発現が、HHV-6の再活性化(HHV-6 DNAの出現)に先行してみとめられたことから、DIHSの早期診断マーカーのとなり得ることが判明した。さらにhhv6b-miR-Ro6-2のレベルが皮疹重症度、発熱期間、DRESS scoreと相関していたことから病勢把握にも役立つ可能性が示された。また、4種類のmicroRNAはそれぞれ異なる発現パターンを示したことから、DIHSの病態において異なる役割を担っている可能性が示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (30 results)

All 2020 2019 2018 2017

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 6 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] Association of HLA-A*11:01 with Sulfonamide-Related Severe Cutaneous Adverse Reactions in Japanese Patients2020

    • Author(s)
      Nakamura R, Ozeki T, Hirayama N, Sekine A, Yamashita T, Mashimo Y, Mizukawa Y, Shiohara T, Watanabe H, Sueki H, Ogawa K, Asada H, Kaniwa N, Tsukagoshi E, Matsunaga K, Niihara H, Yamaguchi Y, Aihara M, Mushiroda T, Saito Y, Morita E
    • Journal Title

      J Invest Dermatol

      Volume: 140 Issue: 8 Pages: 1659

    • DOI

      10.1016/j.jid.2019.12.025

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation Between Expression of CD134, a Human Herpesvirus 6 Cellular Receptor, on CD4+ T cells and Th2-type Immune Responses in Drug-induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms2020

    • Author(s)
      Miyagawa F、Nakamura-Nishimura Y、Kanatani Y、Asada H
    • Journal Title

      Acta Dermato Venereologica

      Volume: - Issue: 6 Pages: adv00102-2

    • DOI

      10.2340/00015555-3465

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs2019

    • Author(s)
      Tashiro Yasuya、Azukizawa Hiroaki、Asada Hideo、Niihara Hiroyuki、Morita Eishin、Yamauchi Teruo、Mizukawa Yoshiko、Kusakabe Yoshio、Numazawa Satoshi、Izumi Miki、Sueki Hirohiko、Watanabe Hideaki
    • Journal Title

      The Journal of Dermatology

      Volume: 46 Issue: 3 Pages: 226

    • DOI

      10.1111/1346-8138.14776

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms or non‐drug‐related erythroderma with a persistent human herpesvirus 6 infection2019

    • Author(s)
      Mitsui Yasuhiro、Ogawa Kohei、Miyagawa Fumi、Azukizawa Hiroaki、Yoshikawa Tetsushi、Asada Hideo
    • Journal Title

      The Journal of Dermatology

      Volume: 47 Issue: 2

    • DOI

      10.1111/1346-8138.15145

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Facial pustules due to drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms may histopathologically mimic eosinophilic pustular folliculitis: A case report.2018

    • Author(s)
      4.Ogawa K, Mitsui Y, Miyamoto S, Nakamura-Nishimura Y, Nakanishi Y, Azukizawa H, Asada H
    • Journal Title

      J Cutan Pathol

      Volume: 印刷中 Issue: 5 Pages: 363-367

    • DOI

      10.1111/cup.13428

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Up-regulation of human herpesvirus 6B-derived microRNAs in the serum of patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms.2018

    • Author(s)
      3.Miyashita K, Miyagawa F, Nakamura Y, Onmori R, Azukizawa H, Asada H
    • Journal Title

      Acta Derm Venereol

      Volume: 98 Issue: 6 Pages: 612-613

    • DOI

      10.2340/00015555-2925

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predisposition to multi-drug hypersensitivity after the administration of mogamulizumab.2018

    • Author(s)
      Miyagawa F, Yamamoto Y, Sugano Y, Ogawa K, Asada H
    • Journal Title

      Eur J Dermatol

      Volume: 28 Issue: 4 Pages: 526-528

    • DOI

      10.1684/ejd.2018.3309

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum thymus and activation-regulated chemokine is associated with the severity of drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome.2018

    • Author(s)
      Nakamura-Nishimura Y, Miyagawa F, Miyashita K, Ommori R, Azukizawa H, Asada H
    • Journal Title

      Br J Dermatol

      Volume: 178 Issue: 6 Pages: 1430-1432

    • DOI

      10.1111/bjd.16132

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mucosal lichen planus mimicking mucosal lesions in Stevens-Johnson syndrome after nivolumab therapy.2018

    • Author(s)
      5.Miyagawa F, Nakajima A, Ohyama S, Aoki Y, Nishikawa M, Nishimura Y, Hashimoto T, Asada H
    • Journal Title

      Acta Derm Venerol

      Volume: 印刷中 Issue: 7 Pages: 687-688

    • DOI

      10.2340/00015555-3185

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ラモトリギン内服開始5ヵ月後に発症し、薬剤性過敏症症候群と類似の病態を呈した薬疹の1例.2018

    • Author(s)
      6.中島 杏奈, 菅野 百加, 小川 浩平, 宮川 史, 小豆澤 宏明, 浅田 秀夫
    • Journal Title

      皮膚の科学

      Volume: 17 Pages: 210-215

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predominant contribution of CD4 T cells to human herpesvirus 6 (HHV-6) load in the peripheral blood of patients with drug-induced hypersensitivity syndrome and persistent HHV-6 Infection.2018

    • Author(s)
      Miyagawa F, Nakamura Y, Ommori R, Miyashita K, Iioka H, Miyashita N, Nishikawa M, Himuro Y, Ogawa K, Asada H
    • Journal Title

      Acta Derm Venereol

      Volume: 98 Issue: 1 Pages: 146-148

    • DOI

      10.2340/00015555-2791

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel interferon-γ enzyme-linked immunoSpot assay using activated cells for identifying hypersensitivity-inducing drug culprits.2017

    • Author(s)
      Kato K, Kawase A, Azukizawa H, Hanafusa T, Nakagawa Y, Murota H, Sakaguchi S, Asada H, Katayama I
    • Journal Title

      J Dermatol Sci

      Volume: 86 Issue: 3 Pages: 222-229

    • DOI

      10.1016/j.jdermsci.2017.03.007

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DIHSの早期診断.2017

    • Author(s)
      浅田秀夫
    • Journal Title

      皮膚アレルギーフロンティア

      Volume: 15 Pages: 77-80

    • Related Report
      2017 Research-status Report
  • [Journal Article] 薬剤性過敏症症候群とTARC2017

    • Author(s)
      浅田秀夫
    • Journal Title

      臨床皮膚科

      Volume: 71 Pages: 66-69

    • Related Report
      2017 Research-status Report
  • [Presentation] The characteristics of patients with persistent HHV-6 infection after drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS).2019

    • Author(s)
      Asada H, Nakamura Y, Miyagawa F, Miyashita K, Shobatake C, Ommori R, Azukizawa H.
    • Organizer
      77th Annual Meeting of SID
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DIHSにおけるウイルス感染と免疫異常2019

    • Author(s)
      浅田秀夫
    • Organizer
      第49回日本皮膚免疫アレルギー学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 薬剤性過敏症症候群のバイオマーカー~血清TARC値の有用性について2019

    • Author(s)
      浅田秀夫
    • Organizer
      第40回日本臨床薬理学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ステロイド治療に抵抗し、皮疹と発熱を繰り返した薬剤性過敏症症候群の一例2019

    • Author(s)
      4.金谷悠司、多良安紀子、有馬亜衣、正畠千夏、小川浩平、宮川史、浅田秀夫
    • Organizer
      第49回日本皮膚免疫アレルギー学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 1.Serum thymus and activation-regulated chemokine(TARC) is a useful marker for assessing the clinical and immunological condition of DRESS/DIHS patients.2018

    • Author(s)
      Nakamura Y, Miyagawa F, Miyashita K, Ommori R, Azukizawa H, Asada H,
    • Organizer
      International Investigative Dermatology 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 2.TARC in drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome(DRESS/DIHS).2018

    • Author(s)
      Asada H
    • Organizer
      The 10th International Congress on Cutaneous Adverse Drug Reactions
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 3.薬剤性過敏症症候群における血清TARC 値の重症度予測マーカーとしての有用性の検討.2018

    • Author(s)
      西村友紀、宮川史、宮下和也、小豆澤宏明、浅田秀夫
    • Organizer
      第117回日本皮膚科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 5.薬剤性過敏症症候群発症後にHHV-6 の持続感染をきたした症例の検討2018

    • Author(s)
      浅田秀夫、西村友紀、宮下和也、宮川史、小豆澤宏明
    • Organizer
      第90回日本皮膚科学会山梨地方会
    • Related Report
      2018 Research-status Report
  • [Presentation] 6.薬剤性過敏症症候群のオーバーラップが疑われたStevens-Johnson 症候群の1 例2018

    • Author(s)
      山本祥子、真柴久実、西川美都子、小川浩平、宮川史、小豆澤宏明、浅田秀夫
    • Organizer
      第48回日本皮膚免疫アレルギー学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 7.薬剤性過敏症症候群発症後にヒトヘルペスウイルス6 の持続感染をきたした症例の検討2018

    • Author(s)
      西村友紀、宮川史、宮下和也、小豆澤宏明、浅田秀夫
    • Organizer
      第48回日本皮膚免疫アレルギー学会
    • Related Report
      2018 Research-status Report
  • [Presentation] HHV-6-derived microRNAs in the serum/ PBMC of DIHS/DRESS patients.2017

    • Author(s)
      Miyashita K, Miyagawa F, Onmori R, Nakamura Y, Azukizawa H, Asada H
    • Organizer
      The 47th Annual ESDR Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Utility of IFN-γ ELISpot assay using anti PD-L1 antibodies for identifying hypersensitivity-inducing drug culprits.2017

    • Author(s)
      Kawase A, Azukizawa H, Kato K, Katayama I, Asada H
    • Organizer
      The 42th Annual Meeting of the Japanease Society for Investigative Dermatology
    • Related Report
      2017 Research-status Report
  • [Presentation] DIHS の経過中にCMV、アスペルギルス感染症を来した症例2017

    • Author(s)
      有馬亜衣、宮下和也、西川美都子、小豆澤宏明、浅田秀夫
    • Organizer
      第116回 日本皮膚科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 薬剤誘発IFN-y ELISpotにおける抗PD-L1抗体の有用性検討2017

    • Author(s)
      河瀬安紗美、小豆澤宏明、加藤健一、片山一朗、浅田秀夫
    • Organizer
      第47回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 薬疹のバイオマーカー2017

    • Author(s)
      浅田秀夫
    • Organizer
      47回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] ガイドライン外来診療20172017

    • Author(s)
      浅田秀夫
    • Total Pages
      663
    • Publisher
      日経メディカル開発
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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