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Studies on host immune responses induced by reactivation of EB virus-infected lymphocytes and resultant skin lesions

Research Project

Project/Area Number 24591653
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionOkayama University

Principal Investigator

IWATSUKI Keiji  岡山大学, 医歯(薬)学総合研究科, 教授 (80126797)

Co-Investigator(Renkei-kenkyūsha) YAMAMOTO Takenobu  川崎医科大学, 医学部, 講師 (50379799)
MORIZANE Shin  岡山大学, 大学病院, 助教 (80423333)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsEBウイルス / 種痘様水疱症 / 蚊刺過敏症 / 慢性活動性EBウイルス感染症 / γδT細胞 / NK細胞 / 遺伝子発現 / 診断キット / 再活性化 / EBウイルス / 慢性活動性EBウイルス感染症 / γδT細胞 / NK細胞 / 予後因子 / 高齢発症 / 血球貪食症候群
Outline of Final Research Achievements

We performed diagnostic examinations on more than 50 cases of EB virus-associated T/NK lymphoproliferative disorders including hydroa vacciniforme (HV), hypersensitivity to mosquito bites (HMB), chronic active EB virus infections(CAEBV) and so on, and studied the pathogenesis. EB virus was found to be infected mainly in gdT cells in classical HV, abT cells in systemic HV, and NK cells in HMB. These results indicate that EB virus-infected lymphocyte subsets are closely related to the clinical phenotypes.
We found prognostic factors in our series of patients: clinical phenotypes, age of the disease onset, and the expression of EB virus reactivation marker, BZLF1. The results suggest that host immune responses against the EBV antigens expressed in the skin lesions induce the severe clinical symptoms. Furthermore, we found elderly patients with atypical HV, and reported their cytological characteristics and EB virus gene expression patterns.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (32 results)

All 2015 2014 2013 2012

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (17 results) (of which Invited: 4 results)

  • [Journal Article] Survival rates and prognostic factors of Epstein-Barr virus-associated hydroa vacciniforme and hypersensitivity to mosquito bites.2015

    • Author(s)
      Miyake T, Yamamoto T, Hirai Y,Otsuka M, Hamada T, Tsuji K, Morizane S, Suzuki D, Aoyama Y, Iwatsuki K
    • Journal Title

      British Journal of Dermatology

      Volume: 172 Issue: 1 Pages: 56-63

    • DOI

      10.1111/bjd.13411

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A patient with elderly-onset atypical hydroa vacciniforme with an indolent clinical course.2015

    • Author(s)
      Nomura H, Suzuki H, Egami S,Yokoyama T, Sugiura M, TomitaK, Imada M, Taniguchi K, Yoshino T, Iwatsuki K
    • Journal Title

      British Journal of Dermatology

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 痂皮も重要な診断材料ーHSV,VZV診断2014

    • Author(s)
      山本剛伸
    • Journal Title

      Visual Dermatology

      Volume: 13 Pages: 626-629

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 塗抹・擦過標本・痂皮から得られる診断のヒント2014

    • Author(s)
      岩月啓氏
    • Journal Title

      Visual Dermatology

      Volume: 13 Pages: 642-645

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current therapy of choice for cutaneous lymphomas: complementary to the JDA/JSCS guidelines.2014

    • Author(s)
      Iwatsuki K, Hamada T, Japan Skin Cancer Society-Lymphoma Study Group
    • Journal Title

      J Dermatol

      Volume: 41 Issue: 1 Pages: 43-49

    • DOI

      10.1111/1346-8138.12346

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epstein-Barr virus-associated T/natural killer-cell lymphomas in the elderly: The first consensus meeting in Kofu2014

    • Author(s)
      Hamada T, Nakamura S, Ko YH, Yoshino T, Ohshima K, Matsuzawa T, Miura K, Takahashi T, Nomura H, Hoshino T, Suzuki D, Shimada S, Iwatsuki K
    • Journal Title

      J Dermatol

      Volume: 41 Issue: 1 Pages: 40-42

    • DOI

      10.1111/1346-8138.12373

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A nationwide study of 1733 patients.2014

    • Author(s)
      Hamada T, Iwatsuki K
    • Journal Title

      J Dermatol

      Volume: 41 Issue: 1 Pages: 3-10

    • DOI

      10.1111/1346-8138.12299

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] An elderly patient with chronic active Epstein-Barr virus infection with severe hydroa vacciniforme-like eruptions associated with αβT-cell proliferation.2014

    • Author(s)
      Nomura H, Egami S, Kasai H, Mori M, Yokoyama T, Fujimoto A, Sugiura M, Iwatsuki K
    • Journal Title

      J Dermatol

      Volume: 41 Issue: 4 Pages: 360-362

    • DOI

      10.1111/1346-8138.12446

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chronic active Epstein-Barr virus infection with progression to large granular lymphocytic leukemia.2013

    • Author(s)
      Komori S, Asai J, Takenaka H, Kuroda J, Hirai Y, Iwatsuki K, Katoh N
    • Journal Title

      J Dermatol

      Volume: 40 Issue: 6 Pages: 487-488

    • DOI

      10.1111/1346-8138.12144

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oculomucosal and gastrointestinal involvement in Epstein-Barr virus-associated hydroa vacciniforme.2012

    • Author(s)
      Yamamoto T, Hirai Y, Miyake T, Yamasaki O, Morizane S, Iwatsuki K
    • Journal Title

      Eur J Dermatol

      Volume: 22 Issue: 3 Pages: 380-383

    • DOI

      10.1684/ejd.2012.1665

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydroa vacciniforme is associated with increased numbers of Epstein-Barrvirus-infected γδT-cells2012

    • Author(s)
      Hirai Y, et al
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 132 Issue: 5 Pages: 1401-1408

    • DOI

      10.1038/jid.2011.461

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proteomic study identified HSP 70kDa protein 1A as a possible therapeutic target, in combination with histone deacetylase inhibitors, for lymphoid neoplasms2012

    • Author(s)
      Fujii K, Suzuki N, Ikeda K, Hamada T,Yamamoto T, Kondo T, Iwatsuki K
    • Journal Title

      JProteomics

      Volume: 75巻 Issue: 4 Pages: 1401-1410

    • DOI

      10.1016/j.jprot.2011.11.010

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phenotypic analysis in a case of hydroa vacciniforme-like eruptions associated with chronic activeEpstein-Barr virus disease of γδ T cells2012

    • Author(s)
      Tanaka C, Hasegawa M, Fujimoto M,Iwatsuki K, Yamamoto T, Yamada K, Kawa K, Saikawa Y, Toga A, Wada T, Takehara K, Yachie A
    • Journal Title

      Br J Dermatol

      Volume: 166巻 Issue: 1 Pages: 216-218

    • DOI

      10.1111/j.1365-2133.2011.10512.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diversity of Epstein-Barr virus BamHI-A rightward transcripts and their expression patterns in the lytic and latent infections2012

    • Author(s)
      Yamamoto T, Iwatsuki K
    • Journal Title

      J Med Microbiol

      Volume: 61巻 Issue: 10 Pages: 1445-1453

    • DOI

      10.1099/jmm.0.044727-0

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Valproic acid inhibits proliferation of EB virus-infectednatural killer cells2012

    • Author(s)
      Fujii K, Suzuki N, Yamamoto T, Duzuki D,Iwatsuki K
    • Journal Title

      Hematology

      Volume: 17巻 Issue: 3 Pages: 163-169

    • DOI

      10.1179/102453312x13376952196494

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 痂皮と水疱蓋を用いた種痘様水疱症と蚊刺過敏症の低侵襲診断的検査の鋭敏度と特異度に関する研究2015

    • Author(s)
      三宅智子、平井陽至、山本剛伸、岩月啓氏
    • Organizer
      第114回日本皮膚科学会学術大会
    • Place of Presentation
      横浜市 パシフィコ横浜
    • Year and Date
      2015-05-29 – 2015-05-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] 種痘様水疱症:分子生物学的手法が実証した記載皮膚科学の確かさ2014

    • Author(s)
      岩月啓氏
    • Organizer
      第438回京滋地方会
    • Place of Presentation
      京都市 メルパルク会館
    • Year and Date
      2014-12-19 – 2014-12-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 皮膚病変から小児造血・組織球系疾患を診る2014

    • Author(s)
      岩月啓氏
    • Organizer
      第56回日本小児血液・がん学会学術集会
    • Place of Presentation
      岡山市 岡山コンベンションセンター
    • Year and Date
      2014-11-29 – 2014-11-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Proposal for nomenclature of EBV-associated T/NK lymphoproliferative disorders: From the cutaneous symptoms and cellular events2014

    • Author(s)
      Keiji Iwatsuki
    • Organizer
      The 113th Annual Meeting of Japanese Dermatological Association: Agora for Asian Dermatologists:Consensus Meeting “EBV-associated Lymphomas”
    • Place of Presentation
      京都市 国立京都国際会館
    • Year and Date
      2014-05-30 – 2014-06-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 皮膚リンパ腫の病期に応じた治療選択2014

    • Author(s)
      岩月啓氏
    • Organizer
      第24回東播磨皮膚科研究会
    • Place of Presentation
      兵庫県加古川市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 髄液より診断し得た自己免疫性水疱症に対して免疫抑制療法中に発症したEBV関連中枢原発悪性リンパ腫の1例2014

    • Author(s)
      三宅智子、木村摩耶、山口麻里、野田和代、濱田利久、青山裕美、岩月啓氏
    • Organizer
      第37回LCH研究会・第23回EBウイルス感染症研究会
    • Place of Presentation
      東京都千代田区
    • Related Report
      2013 Research-status Report
  • [Presentation] Epidemiology of cutaneous lymphoma in Japan: A nationwide study of 1,871 patients2013

    • Author(s)
      Hamada T, Iwatsuki K
    • Organizer
      2013 International Investigative Dermatology Meeting
    • Place of Presentation
      Edinburgh, UK
    • Related Report
      2013 Research-status Report
  • [Presentation] Pathogenic cell types, molecular mechanisms and prognostic factors in EB virus-associated cutaneous T/NK lymphoproliferative disorders2013

    • Author(s)
      Iwatsuki K, Miyake T, Hirai Y, Yamamoto T, Fujii K, Suzuki D, Tsuji K, Morizane S
    • Organizer
      2013 International Investigative Dermatology Meeting
    • Place of Presentation
      Edinburgh, UK
    • Related Report
      2013 Research-status Report
  • [Presentation] Eradication of cutaneous herpesvirus infections by nucleic acid sensors and cytotoxic T lymphocyte-mediated apoptotic processes2013

    • Author(s)
      Hirai Y, Yamamoto T, Morizane S, Miyake T, Takiguchi T, Iwatsuki K
    • Organizer
      2013 International Investigative Dermatology Meeting
    • Place of Presentation
      Edinburgh, UK
    • Related Report
      2013 Research-status Report
  • [Presentation] γδT細胞(EBV陽性)の著明な増多を認めた種痘様水疱症の1例2013

    • Author(s)
      山田朋子、飯田絵理、小山尚俊、塚原理恵子、中村考伸、中村哲史、渡邉萌理、梅本尚可、加倉井真樹、出光俊郎、野口義久、三宅智子、岩月啓氏
    • Organizer
      第112回日本皮膚科学会総会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] 高齢発症した重症型種痘様水疱症、慢性活動性EBウイルス感染症の1例2013

    • Author(s)
      野村尚志、江上将平、笠井弘子、森 真理子、藤本篤嗣、杉浦 丹、岩月啓氏
    • Organizer
      第29回日本皮膚悪性腫瘍学会学術大会
    • Place of Presentation
      山梨県甲府市
    • Related Report
      2013 Research-status Report
  • [Presentation] Extranodal NK/T cell lymphoma、nasal typeにおけるT細胞受容体δ鎖の遺伝子再構成に関する検討2013

    • Author(s)
      鈴木大介、長尾 洋、岩月啓氏
    • Organizer
      第29回日本皮膚悪性腫瘍学会学術大会
    • Place of Presentation
      山梨県甲府市
    • Related Report
      2013 Research-status Report
  • [Presentation] 種痘様水疱症皮疹を生じるadult-onset例:early-onsetおよびelderly-onset例との比較2013

    • Author(s)
      平井陽至、山本剛伸、三宅智子、岩月啓氏
    • Organizer
      第29回日本皮膚悪性腫瘍学会学術大会
    • Place of Presentation
      山梨県甲府市
    • Related Report
      2013 Research-status Report
  • [Presentation] 自己免疫性水疱症に対する免疫抑制療法中に発症した致死性EBウイルス関連中枢性リンパ腫2013

    • Author(s)
      木村摩耶、三宅智子、山口麻里、野田和代、濱田利久、青山裕美、岩月啓氏、山本剛伸
    • Organizer
      第65回日本皮膚科学会西部支部学術大会
    • Place of Presentation
      鹿児島県鹿児島市
    • Related Report
      2013 Research-status Report
  • [Presentation] Immediate-early gene reactivation signal, BZLF1 expression, is a molecular marker for a poor prognosis of Epstein-Barr virus-associated T/NK lymphoproliferative skin diseases2013

    • Author(s)
      Iwatsuki K, Yamamoto T, Hirai Y, Miyake T
    • Organizer
      2nd World Congress of Cutaneous Lymphomas/ 6th International Symposium on the Biology and Immunologu of Cutaneous Lymphoma
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Research-status Report
  • [Presentation] Remodeling of the cutaneous immune system and structures during viral infections2013

    • Author(s)
      Iwatsuki K
    • Organizer
      The 23rd Annual Meeting of Korean Society for Investigative Dermatology
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Remodeling of the skin immune system during viral infections2012

    • Author(s)
      Iwatsuki K
    • Organizer
      3rd Skin Physiology International Meeting (SPIM)
    • Place of Presentation
      Vichy, France
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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