Research on the pathogenesis and treatment of Epstein-Barr virusassociated intractable diseases

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyushu University
• Principal Investigator: OHGA Shouichi 九州大学, 医学研究院, 教授 (60233053)
• Co-Investigator(Kenkyū-buntansha): TANAKA Tamami 九州大学, 医学(系)研究科(研究院), 学術研究員 (60423547)
• Co-Investigator(Renkei-kenkyūsha): IMADOME Ken-ichi 国立成育医療センター研究所, 母児感染研究部, 感染防御研究室室長 (70392488) ; OHSHIMA Koichi 久留米大学医学部, 第2病理学教室, 教授 (50203766)
• Project Period (FY): 2009 – 2011
• Keywords: 小児感染症学

Research Abstract

In patients with chronic active Epstein-Barr virus infection(CAEBV) or EBVassociated hemophagocytic syndrome(EBV-HLH), EBVpositive T/NK cells were suggested to arise from hematopoietic progenitors and need CD4positive cells for the clonal proliferation in a distinct manner from tumorigenesis. Early immunomodulatory therapy effectively controlled EBV-HLH in children with primary infection. Long-term outcomes of pediatric patients were favorable after hematopoietic stem cell transplantation, while adult patients had poor outcomes. Characterization of EBVinfected T/NK cells is critical for the establishment of treatment strategy.

Research Products

• [Journal Article] Reducedintensity conditioning in unrelated donor cord blood transplantation for patients with familial hemophagocytic lymphohistiocytosis (2012)
  • Author(s): Nishi M, Nishimura R, Suzuki N, Sawada A, Okamura T, Fujita N, Kanai R, Yano J, Adachi S, Yasumi T, Sate E, Yasutomo K, Ishii E, Ohga S
  • Journal Title: Am J Hematol
  • Peer Reviewed
• [Journal Article] Acute liver failure as the initial manifestation of Wilson disease trigerred by human parvovirus Big infection (2012)
  • Author(s): Shiraishi A, Hoshina T, Ihara K, Doi T, Ohga S, Hara T
  • Journal Title: Pediatr Infect Dis J Volume: 31(1) Pages: 103-104
  • Peer Reviewed
• [Journal Article] CD4+ T cells have a critical role in the proliferation of EBVinfected T and NK cells (2012)
  • Author(s): Imadome K, Yajima M, Alai A, NakagawaNakazawa A, Kawano F, Ichikawa S. Shimizu N, Yamamoto N, Morie T, Ohga S, Nakamura H, Ito M, Miura 0, Komano J, Fujiwara S
  • Journal Title: PLOS Pathogen
  • Peer Reviewed
• [Journal Article] Treatment choice of immunotherapy or further chemotherapy for Epstein-Barr virusassociatedhemophagocytic lymphohistiocytosis (2012)
  • Author(s): Shiraishi A, Ohga S, Dol T, Ishimura M, Takimoto T, Takada H, Miyamoto T, Abe Y, Hara T
  • Journal Title: Pediatr Blood Cancer
  • Peer Reviewed
• [Journal Article] 血球貪食症候群hemophoagocytis syndrome特集知っておきたい内科症候群,内科 (2012)
  • Author(s): 大賀正一
  • Volume: 109巻6号増大号
• [Journal Article] Clonal origin of Epstein-Barr virus(EBV) infected T/NK-cell subpopulations in EBVpositive T/NK-cell lymphoproliferative disorders of childhood (2011)
  • Author(s): Ohga S, Ishimura M, Yoshimoto G, Miyamoto T, Takada H, Tanaka T, Ohshima K, Ogawa Y, lmadome K, Abe Y, Akashi K, Hara T
  • Journal Title: J Crin viral Volume: 51(1) Pages: 31-37
  • Peer Reviewed
• [Journal Article] Potent induction of IFN-y production from cord blood NK cells by the stimulation with singlestrand RNA (2011)
  • Author(s): Eljaafari FM, Takada H, Tanaka T, Dol T, Ohga S, Hara T
  • Journal Title: J Crin Immunol Zot Volume: 31(4) Pages: 728-735
  • Peer Reviewed
• [Journal Article] Hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation in children : a nationwide survey in Japan (2011)
  • Author(s): 柊sa no T, Kogawa K, Morimoto A, Ishida Y, Suzuki N, Ohga S, Kudo K, Ohta S, Wakiguchi H, Tabuchi K, Kate S, Ishii E
  • Journal Title: Pediatr Blood Cancer
  • Peer Reviewed
• [Journal Article] ExtensivegenedeletionsinJapanesepatientswithDiamond-Blackfan anemia (2011)
  • Author(s): KuramitsuM, MatsubaraA, MorioT, TakagiM, TokiT, TeruiK, RuNanW, KannoH, Ohga S, OharaA, KitohT, SugitaK, KudoK, MatsubayashiT, MizueN, OzekiM, MasumiA, MomoseH, TakizawaK, MizukamiT, YamaguchiK, OgawaS, ItoE, HamaguchiI
  • Journal Title: Blood
  • Peer Reviewed
• [Journal Article] Recurrentat riall fibrillation after high-dose methylprednisolone therapy in a girl with lupusassociated hemophagocytic syndrome (2011)
  • Author(s): Yamamura K, Ohga S, Nishiyama K, Doi T, Tsutsumi Y, Ikeda K, Fujishima A, Takada H, Hara T
  • Journal Title: Lupus Volume: 20(8) Pages: 871-875
  • Peer Reviewed
• [Journal Article] Serum prohepcidin concentrations at birth and one month after birth in premature infants (2011)
  • Author(s): Kitajima J, Ohga S, Kinjo T, Ochiai M, Takahata Y, Honjo S, Hara T
  • Journal Title: Pediatric Blood & Cancer Volume: 56 Pages: 267-272
  • Peer Reviewed
• [Journal Article] ウイルス感染と免疫異常 (2011)
  • Author(s): 大賀正一
  • Journal Title: IIウイルス感染と免疫障害EBウイルス、臨床とウイルス Volume: 39巻 Pages: 33-38
  • Peer Reviewed
• [Journal Article] EBウイルス感染TINK細胞リンパ増殖症～臨床病態と感染標的細胞～ (2011)
  • Author(s): 大賀正一
  • Journal Title: 福岡医学雑誌 Volume: 102巻 Pages: 41-47
  • Peer Reviewed
• [Journal Article] 血球貪食症候群の発症機構に迫る4. EBV関連血球食食症候群 (2011)
  • Author(s): 土居岳彦、大賀正一
  • Journal Title: 医学のあゆみ Volume: 238巻 Pages: 1053-1057
• [Journal Article] 血球貪食症候群の病態と治療update遺伝性血球貪食症候群の発症機序 (2011)
  • Author(s): 大賀正一
  • Journal Title: 血液内科 Volume: 63巻5号 Pages: 640-643
• [Journal Article] Incomplete Kawasaki disease in a patient with chronic granulomatous disease (2010)
  • Author(s): Muneuchi J, Ishimura M, Takada H, Hoshina T, Utsunomiya R, Ikeda K, Yamaguchi K, Ohga S, Kusuhara K, Hara T
  • Journal Title: Pediatr Int Volume: 52(3) Pages: 134-136
  • Peer Reviewed
• [Journal Article] Improved outcome of refractory Langerhans cell histiocytosis in children with hematopoietic stem cell transplantation in Japan (2010)
  • Author(s): Kudo K, Ohga S, Morimoto A, Ishida Y, Suzuki N, Hasegawa D, Nagatoshi Y, Kate S, Ishii E
  • Journal Title: Bone Marrow Transplant Volume: 45 Pages: 901-906
  • Peer Reviewed
• [Journal Article] Mutations in the ribosomal protein genes in Japanese patients with DiamondBlackfan anemia (2010)
  • Author(s): Konno Y, Toki T, Tandai S, Xu G, Wang R, Terui K, Ohga S, Hara T, Hama A, Kojima S, Hasegawa D, Kosaka Y, Yanagisawa R, Koike K, Kanai R, Imai T, Hongo T, Park MI, Sugita K, Ito E
  • Journal Title: Haematologica Volume: 95 Pages: 1293-1299
  • Peer Reviewed
• [Journal Article] NEMO mutation as a cause of familial occurrence of Behcet' s disease in female patients (2010)
  • Author(s): Takada H, Nomura A, Ishimura M, Ichiyama M, Ohga S, Hara T
  • Journal Title: Crin Genet Volume: 78 Pages: 575-579
  • Peer Reviewed
• [Journal Article] Hepatitisassociated aplastic anemia during a primary infection of genotype 1 a torque teno virus (2010)
  • Author(s): Ishimura M, Ohga S, Ichiyama M, Kusuhara K, Takada H, Hara T, Takahashi M, Okamoto H
  • Journal Title: Eur J Pediatr Volume: 169 Pages: 899-902
  • Peer Reviewed
• [Journal Article] Stem cell transplantation for pediatric malignancy Hemophagocytic lymphohistiocytosis (2010)
  • Author(s): Ohga S, Ishii E, Takada H, Hara T
  • Journal Title: 15th Congress of AsiaPacific Blood and Marrow Transplantation Pages: 71-76
• [Journal Article] Nationwide survey of singlesystem single site Langerhans cell histiocytosis in Japan (2010)
  • Author(s): Morimoto A, Ishida Y, Suzuki N, Ohga S, Shioda Y, Okimoto Y, Kudo K, Ishii E
  • Journal Title: Pediatric Blood Cancer Volume: 54(1) Pages: 98-102
  • Peer Reviewed
• [Journal Article] Hematopoietic stem cell transplantation for familial hemophagocytic lymphohistiocytosis and Epstein-Barr virusassociated hemophagocytic lymphohistiocytosis in Japan (2010)
  • Author(s): Ohga S, Kudo K, Ishii E, Honjo S, Morimoto A, Osugi Y, Sawada A, Tabuchi T, Suzuki N, Ishida Y, Imashuku S, Kate S, Hara T
  • Journal Title: Pediatric Blood Cancer Volume: 54(2) Pages: 299-306
  • Peer Reviewed
• [Journal Article] 成人EBウイルス関連血球貪食症候群5例の検討 (2010)
  • Author(s): 安部康信、白土基明、永澤恵理子、大塚理恵、喜安純一、佐田絵里子、井筒挙策、古藤和浩、西村純二、大賀正一、高柳涼一
  • Journal Title: 臨床血液 Volume: 51巻 Pages: 74-79
  • Peer Reviewed
• [Journal Article] 特集企画血液疾患の診かた一血液専門医以外のための血液疾患対応マニュアルー血球貧食症候群 (2010)
  • Author(s): 大賀正一
  • Journal Title: プライマリ・ケア医のための総合誌「治療」 Volume: 92巻 Pages: 2401-2406
• [Journal Article] Fulminant sepsis/meningitis due to Haemophilus influenzae in a protein Cdeficient heterozygote treated with activated protein C therapy (2009)
  • Author(s): Ishimura M, Saito M, Ohga S, Hoshina T, Baba H, Urata M, Kira R, Takada H, Kusuhara K, Kang D, Hara T
  • Journal Title: Eur J Pediatr Volume: 168(6) Pages: 673-677
  • Peer Reviewed
• [Journal Article] Cardiovascular complications associated with chronic active Epstein-Barr virus infection (2009)
  • Author(s): Muneuchi J, Ohga S, Ishimura M, Ikeda K, Yamaguchi K, Nomura A, Takada H, Abe Y, Hara T
  • Journal Title: Pediatr Cardiol Volume: 30(3) Pages: 274-281
  • Peer Reviewed
• [Journal Article] Characteristicsofhemophagocyticlymphohistiocytosisinneonates:anationwidesurveyinJapan (2009)
  • Author(s): SuzukiN, MorimotoA, Ohga S, KudoK, IshidaYlIshii E
  • Journal Title: JPediatr Volume: 155(2) Pages: 235-238
  • Peer Reviewed
• [Journal Article] Neonatal onset hemophagocytic lymphohistiocytosis in a premature infant (2009)
  • Author(s): KatsuragiS, Ohga S, HoriuchiH, HaraT, TeraoK, IkedaT
  • Journal Title: Pediatr Blood Cancer Volume: 53(2) Pages: 244-245
  • Peer Reviewed
• [Journal Article] 免疫不全症候群と遺伝子異常各疾患の遺伝子異常,診断と治療家族性血球貧食症候群 (2009)
  • Author(s): 大賀正一、田中珠美
  • Journal Title: 臨床検査 Volume: 53巻 Pages: 599-604
• [Journal Article] 小児疾患診療のための病態生理血液・腫瘍性疾患血球貪食症候群 (2009)
  • Author(s): 大賀正一
  • Journal Title: 小児内科増刊号 Volume: 41巻 Pages: 1197-1202
• [Presentation] Diagnostic usefulness of the expression levels of interferonstimulated genes in histiocytic necrotizing lymphadenitis (2011)
  • Author(s): shimura M, Mizuno Y, Takada H, Doi T, Ohga S, Hara T
  • Organizer: M 40回日本免疫学会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 20111127-02
• [Presentation] 家族性血球貧食性リンパ組織球症(FHL)に対する前処置軽減非血縁膀帯血移植(RIC-UCBT)' (2011)
  • Author(s): 西眞範、西村良成、鈴木信寛、岡村隆行、矢野潤、足立壮一、八角高裕、佐藤恵実子、金井理恵、藤田直人、澤田明久、石井榮一、大賀正一
  • Organizer: 第53回日本小児血液・がん学会学術集会2011
  • Place of Presentation: 前橋
  • Year and Date: 20111125-273
• [Presentation] EBウイルス関連血球貧食性リンパ組織球症(EBV」HLH)の治療選択:単一施設の解析から (2011)
  • Author(s): 白石暁、土居岳彦、大賀正一、石村匡崇、瀧本智仁、高田英俊、宮本敏浩、安部康信、原寿郎
  • Organizer: 第53回日本小児血液・がん学会学術集会
  • Place of Presentation: 前橋
  • Year and Date: 20111125-27
• [Presentation] Unrelated cord Blood Transplantation for familial hemophagocytic lymphohistiocytosis(FHL) (2011)
  • Author(s): Ohga S, Nishi M, Nishimura R, Suzuki N, Okamura T, Yano J, Adachi S, Sato E, Kanai R, Sawada A, Ishii E
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] Characteristic presentation of congenital protein C(PC) deficiency in childR) od (2011)
  • Author(s): Ohga S, Kinjo T, Matsunaga Y, Ochiai M, Doi T, Ishimura M, Yamamoto Y, Suenobu S, Shirahata A, Urata M, Kayamori Y, Kang D, Hara T
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] Treatment outcomes of EB virusassociatedhemophagocytic lymphohistiocytosis in a single institution (2011)
  • Author(s): Shiraishi A, Doi T, Ohga S, Ishimura M, Takimoto T, Takada H, Miyamoto T, Abe Y, Hara T
  • Organizer: 73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] High levels of human cytokines were detected in a novel mouse xenograft model of CAEBV and EBV-HLH' (2011)
  • Author(s): Yamada C, Imadome K, Arai A, Nakazawa A, Kawano F, Ichikawa S, Shimizu N, Yamamoto N, Morio T, Ohga S, Ito M, Koyama T, Miura 0, Komano J, Fujiwara S
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20111014-16
• [Presentation] 慢性活動性EBウイルス感染症におけるEBV感染T/NK細胞クローンの起源 (2011)
  • Author(s): 大賀正一、石村匡崇、土居岳彦、瀧本智仁、高田英俊、原寿郎
  • Organizer: 第114回日本小児科学会学術集会2011
  • Place of Presentation: 東京
  • Year and Date: 20110812-14
• [Presentation] Congenital protein C deficiency in the Japanese experience The 7th Congress of ASPR, Hematology Session" Thrombosis in Children in the West and East" (2011)
  • Author(s): Ohga S
  • Organizer: Pediatric Academic Societies(PAS) and Asian Society for Pediatric Research(ASPR) 2011 Joint Meeting
  • Place of Presentation: Colorado, USA
  • Year and Date: 20110430-0503
• [Presentation] 血球貪食症候群に対する治療戦略 (2011)
  • Author(s): 大賀正一
  • Organizer: 第62回日本小児科学会佐賀地方会(招待講演)
  • Place of Presentation: 佐賀
  • Year and Date: 2011-12-03
• [Presentation] Hemophagocytic lymphohistiocytosis. Education Session IV Hematopoietic stem cell transplantation for pediatric malignant diseases (2010)
  • Author(s): Ohga S
  • Organizer: The 15th Congress of AsiaPacific BMT(招待講演)
  • Place of Presentation: Phuket
  • Year and Date: 20101029-31
• [Presentation] hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation in children : nationwide survey of Japan (2010)
  • Author(s): Asano T, Kogawa K, Morimoto A, Ishida Y, Suzuki N, Ohga S, Kudo K, Ohta S, Wakiguchi H, Tabuchi K, Kato S, Ishii E, The HLH/LCH and SCT committees in the Japanese Society of Pediatric Hematology
  • Organizer: The 27th Annual Meeting of Histiocyet Society
  • Place of Presentation: Boston, USA
  • Year and Date: 20101018-20
• [Presentation] Clonal origin of EBVinfected T/NK-cell subpopulations in chronicactive Epstein-Barr virus infection (2010)
  • Author(s): Ohga S, Takada H, Abe Y, Miyamoto T, Akashi K, Ohshima K, Hara T
  • Organizer: The 6th Workshop of Asian Hematology in Bangkok NRCT-JSPS Asian Core Program
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2010-12-23
• [Presentation] Hematopoietic stem cell transplantation for HLH/LCH, and a review of neonatal hemophagocytic lymphohistiocytosis in Japan (2010)
  • Author(s): Ohga S
  • Organizer: The 4th Seminar on Histiocytosis & Pediatric MDS(招待講演)
  • Place of Presentation: Korea
  • Year and Date: 2010-10-07
• [Presentation] Clonal origin of EB virusinfected T/NK-cells in chronic active EB virus infection (2010)
  • Author(s): Ohga S, Ishimura M, Doi T, Takada H, Yoshimoto G, Miyamoto T, Abe Y, Imadome K, Ohshima K, Akashi K, Hara T
  • Organizer: 横浜第72回日本血液学会
  • Year and Date: 2010-09-25
• [Presentation] Four adult cases of chronic active Epstein-Barr virus(EBV) infection (2010)
  • Author(s): Abe Y, Shiratsuchi M, Nagasawa E, Ohno H, Sada E, Ohba R, Matsushima T, Ohga S, Takayanagi R, Ohshima K
  • Organizer: 第72回日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Hemophagocytic lymphohistiocytosis after stem cell transplantation in children : nationwide survey (2010)
  • Author(s): Asano T, Kogawa K, Morimoto A, Ishida Y, Suzuki N, Ohga S, Kudoh K, Ohta S. Wakiguchi H, Tabuchi K, Katoh S, Ishii E
  • Organizer: 第72回日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] EBV関連および家族性血球貪食性リンパ組織球症に対する造血細胞移植の成績 (2009)
  • Author(s): 大賀正一、工藤寿子、森本哲、大杉夕子、澤田明久、田淵健、本荘哲、原寿郎、加藤俊一、石井榮一
  • Organizer: 第112回日本小児科学会
  • Place of Presentation: 奈良
  • Year and Date: 20090417-19
• [Book] 診断と治療社、小児の発熱AtoZ-診断 治療のTipsとPit魚lls-52.慢性活動性EBウイルス感染症 (2012)
  • Author(s): 大賀正一
  • Publisher: CAEBV(印刷中)
• [Book] 免疫疾患慢性活動性EBウイルス感染症、総合小児科診療のための小児科学レビュー (2010)
  • Author(s): 土居岳彦、大賀正一、原寿郎
  • Total Pages: 184-190