Human herpesvirus-6 encephalitis after allogeneic stem cell transplantation: analysis of pathologic condition to predict the development.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591422
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Oita University
• Principal Investigator: OGATA Masao 大分大学, 医学部, 講師 (10332892)
• Co-Investigator(Kenkyū-buntansha): SATOU Takako 大分大学, 医学部, 研究補佐員 (90420645) ; KOHNO Kazuhiro 大分大学, 医学部, 助教 (80420644) ; KADOTA Jun-ichi 大分大学, 医学部, 教授 (50233838) ; TAKANO Kuniko 大分大学, 医学部, 特任助教 (20617427)
• Project Period (FY): 2011 – 2013
• Keywords: 造血細胞移植 / ヒトヘルペス6 / ヒトヘルペス6脳炎 / サイトカイン

Research Abstract

To elucidate the immunological pathogenesis of human herpesvirus (HHV)-6 encephalitis, we performed detailed cytokine study against 172 HCT recipients, including 20 patients with HHV-6 encephalitis. Seventeen kinds of cytokines in plasma samples collected weekly until 28 days after HCT, and cerebrospinal fluid (CSF) at the time of developing HHV-6 encephalitis were measured. The plasma IL-8, -10, -13, MCP-1, and MIP-1b were significantly higher in patients who developed HHV-6 encephalitis than those without HHV-6 encephalitis. High-level IL-6 predicted poor prognosis for patients with HHV-6 encephalitis. Among patients with HHV-6 encephalitis, IL-5, -6, and -8 in CSF were higher in patients who progress to severe status (died of encephalitis or sequelae) than in other patients. We suggest that several cytokines mediate the pathogenesis of HHV-6 encephalitis. Increased levels of cytokines in plasma and CSF predict development and poor prognosis of HHV-6 encephalitis.

Research Products

• [Journal Article] Risk factors for human herpesvirus 6 reactivation and its relationship with syndrome of inappropriate antidiuretic hormone secretion after stem cell transplantation in pediatric patients (2013)
  • Author(s): Toriumi N, Kobayashi R, Yoshida M, Iguchi A, Sarashina T, Okubo H, Suzuki D Sano H, Ogata M, Azuma H
  • Journal Title: J Pediatr Hematol Oncol Volume: (Epub ahead of print)
• [Journal Article] Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation : a multicenter, prospective study (2013)
  • Author(s): Ogata M, Satou T, Kadota J, Saito N, Yoshida T, Okumura H, Ueki T, Nagafuji K, Kako S, Uoshima N, Tsudo M, Itamura H, Fukuda T
  • Journal Title: Clin Infect Dis Volume: 57 Pages: 671-681
• [Journal Article] Foscarnet against human herpesvirus (HHV) -6 reactivation after allo-SCT : breakthrough HHV-6 encephalitis following antiviral prophylaxis (2013)
  • Author(s): Ogata M, Satou T, Inoue Y, Takano K, Ikebe T, Ando T, Ikewaki J, Kohno K, Nishida A, Saburi M, Miyazaki Y, Ohtsuka E, Saburi Y, Fukuda T, Kadota J
  • Journal Title: Bone Marrow Transplant Volume: 48 Pages: 257-264
• [Journal Article] Chromosomally integrated human herpesvirus 6: questions and answers (2012)
  • Author(s): Pellett PE, Ablashi DV, Ambros PF, Agut H, Caserta MT, Descamps V, Flamand L, Gautheret-Dejean A, Hall CB, Kamble RT, Kuehl U, Lassner D, Lautenschlager I, Loomis KS, Luppi M, Lusso P, Medveczky PG, Montoya JG, Mori Y, Ogata M, Pritchett JC, Rogez S, Seto E, Ward KN, Yoshikawa T, Razonable RR
  • Journal Title: Rev Med Virol Volume: 22 Pages: 144-155
• [Presentation] Saliva as a potential route of virus entry into the CNS in HV-6 encephalitis after allogeneic HCT (2013)
  • Author(s): Takata H, Ogata M, Satou T, Honda S, Yoshida N, Nashimoto Y, Moroga Y, Takano K, Ikebe T, Kohno K, shirao K, Kadota J, Ueki T, Kobayashi H, Takeda W, Kirihara T, Sato K, Fujiwara Y, Shimizu I, Hiroshima Y, Sumi M
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2013-10-11
• [Presentation] Correlations of cytokine concentration in plasma and CSF with outcome of HHV-6 encephalitis (2013)
  • Author(s): Takano K, Ogata M, Satou T, Shirao K, Kadota J, Miyazaki Y, Saitou N, Ueki T, Okumura H, Nagafuji K, Kako S, Uoshima N, Fukuda T
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2013-10-11
• [Presentation] Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation : a multicenter, prospective study (2013)
  • Author(s): Ogata M, Satou T, Kadota J, Saito N, Yoshida T, Okumura H, Ueki T, Nagafuji K, Kako S, Uoshima N, Tsudo M, Itamura H, Fukuda T
  • Organizer: 18^<th> Congress of the European Hematology Association
  • Place of Presentation: Stockholm
  • Year and Date: 2013-06-13
• [Presentation] 同種造血細胞移植後HHV-6脳炎 (2013)
  • Author(s): 緒方正男
  • Organizer: 第35回日本造血細胞移植学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2013-03-07
• [Presentation] 同種造血細胞移植におけるHHV-6感染症: HHV-6脳炎を中心として (2012)
  • Author(s): 緒方正男
  • Organizer: 第60回日本化学療法学会西日本支部総会、第55回日本感染症学会中日本地方会学術集会、第82回日本感染症学会西日本地方会
  • Place of Presentation: 福岡
  • Year and Date: 2012-11-05
  • Invited
• [Presentation] Multicenter prospective study of HHV-6 reactivation and its effect on CNS after allogeneic SCT (2012)
  • Author(s): Ogata M, Satou T, Kadota J, Saito M, Ueki T, Yoshida T, Okumura H, Nagafuji K, Kako S, Uoshima N, Tsudo M, Ichinohe T, Fukuda T
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-20
• [Presentation] 同種造血細胞移植後HHV-6脳炎 (2012)
  • Author(s): 緒方正男
  • Organizer: 第17回日本神経感染症学会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-19
  • Invited
• [Presentation] 同種造血細胞移植後HHV-6脳炎:解明と克服に向けて (2012)
  • Author(s): 緒方正男
  • Organizer: 第27回ヘルペスウイルス研究会
  • Place of Presentation: あいち健康プラザ
  • Year and Date: 2012-06-07
  • Invited
• [Presentation] 同種造血細胞移植後human herpesvirus-6 (HHV-6)脳炎の発症にはHHV-6再活性化のレベルとIL-6高値が関連する (2012)
  • Author(s): 高野久二子、緒方正男、井上佑子、門田淳一、佐分利益穂、佐分利能生
  • Organizer: 第86回日本感染症学会総会
  • Place of Presentation: 長崎
  • Year and Date: 2012-04-25
• [Presentation] 同種造血細胞移植後HHV-6再活性化のモニタリングにおける、血漿及び全血を用いたreal-time PCR法の比較 (2012)
  • Author(s): 井上佑子、緒方正男、高野久二子、門田淳一、佐分利益穂、佐分利能生
  • Organizer: 第86回日本感染症学会総会
  • Place of Presentation: 長崎
  • Year and Date: 2012-04-25
• [Presentation] 同種造血細胞移植後HHV-6脳炎 (2012)
  • Author(s): 緒方正男
  • Organizer: 第34回日本造血細胞移植学会
  • Place of Presentation: 大阪市
  • Year and Date: 2012-02-24
  • Invited
• [Presentation] High plasma IL-6 level before HHV-6 reactivation is key factors of HHV-6 encephalitis development (2011)
  • Author(s): Takano K, Ogata M, Satou T, Inoue Y, Moroga Y, Ikebe T, Ando T, Ikewaki J, Kohno K, Saburi M, Nishida A, Miyazaki Y, Ohtsuka E, Saburi Y, Kadota J
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] Plasma human herpesvirus 6 (HHV-6) DNA loads and interleukin-6 concentration as factors in the development of HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation (2011)
  • Author(s): Takano K, Satou T, Ogata M, Ikewaki J, Kohno K, Miyazaki Y, Ohtsuka E, Saburi Y,Kadota J
  • Organizer: The 16^<th> Congress of European Hematology Association
  • Place of Presentation: London
  • Year and Date: 2011-06-10
• [Book] Human herpesviruses HHV-6A, HHV-6B & HHV-7. Chapter 13. Zerr DM & Ogata M. HHV-6A and HHV-6B in recipients of hematopoietic cell transplantation
  • Author(s): Flammand L, Lautenschlager I, Krueger G, Ablashi E (編)
  • Total Pages: 217-234
  • Publisher: Elsevier Science