慢性活動性EBウイルス感染症の感染細胞特性と治療に関する研究

2008 Fiscal Year Annual Research Report

• Project/Area Number: 19591255
• Research Institution: Kyushu University
• Principal Investigator: 大賀 正一 Kyushu University, 大学病院, 准教授 (60233053)
• Co-Investigator(Kenkyū-buntansha): 宮本 敏浩 九州大学, 大学病院, 講師 (70343324) ; 田中 珠美 九州大学, 医学研究院, 学術研究員 (60423547)
• Keywords: EBウイルス / リンパ増殖性疾患 / 感染細胞 / 免疫不全症

Research Abstract

慢性活動性EBウイルス感染症(Chronic active Epstein-Barr virus infection:CAEBV)患者の治療確立をめざして、自験例の合併症と治療成績およびEBV持続感染細胞(T/NK細胞)の特性を解析した。造血幹細胞移植が唯一の根治療法である本症の3大臓器病変は、神経、心血管および腸管である。神経合併症については、神経症状のない時期から脳脊髄液にEBV量が上昇している例があり、末梢血よりも脳脊髄液でEBV量が高い値を示すこと、これが中枢神経におけるEBV再活性化と感染細胞の浸潤を示唆することを文献報告した。心合併症例については、冠動脈病変が造血幹細胞移植後に感染細胞を排除できた2例において正常化したことを文献報告した。EBV関連血球貪食症候群の重症例に対する移植成績をCAEBVと比較して文献報告し、さらに家族性血球貪食症候群との比較を全国調査に広げて解析した結果を国際学会で報告し、投稿した。これらの報告は、骨髄非破壊的移植と非血縁臍帯血移植を組み合わせることが今後の治療成績向上に結びつく可能性の高いことを示唆するものである。さらに、CAEBV6例(T細胞型3例、NK細胞型3例、造血細胞移植3例を含む)について、患者のリンパ球亜群におけるEBV感染の様式を高純度細胞分離(>99.9%)により解析し、T細胞型でもNK細胞に、NK細胞型でもT細胞に感染があり、さらにこれらもクローン増殖している例は半数以上あることを確認した。前駆細胞レベルでの感染が示唆される症例もあったが骨髄幹細胞に感染している例はなかった。以上の解析を終了した。

Research Products

• [Journal Article] Characteristics of hemophagocytic lymphohistiocytosis in neonates : a nationwide survey in Japan (2009)
  • Author(s): Suzuki N, Morimoto A, Ohga S, Kudo K, Ishida Y, Ishii E
  • Journal Title: J Pediatr (未定)(in press)
  • 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 (未定)(in press)
  • Peer Reviewed
• [Journal Article] Fulminant sepsis/meningitis in a protein C-deficient 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, Kane D, Hara T
  • Journal Title: Eur J Pediatr (未定)(in press)
  • Peer Reviewed
• [Journal Article] Neonatal onset hemophagocytic lymphohistiocytosis in a premature infant (2009)
  • Author(s): Katsuragi S, Ohga S, Horiuchi H, Hara T, Terao K, Ikeda T
  • Journal Title: Pediatr Blood Cancer (未定)(in press)
  • Peer Reviewed
• [Journal Article] Disseminated Bacillus Calmette-Guerin lymphadenitis in a patient with gp91phox-chronic granulomatous disease 25 years after vaccination (2009)
  • Author(s): Kusuhara K, Ohga S, Hoshina T, Saito M, Sasaki Y, Ishimura M, Takada H, Fujita M, Hara T
  • Journal Title: Eur J Pediatr (未定)(in press)
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus load in cerebrospinal fluid of patients with chronic active Epstein-Barr virus infection (2008)
  • Author(s): Ohga S, Sanefuji M, Ishimura M, Nomura A, Torisu H, Kira R, Takada H, Mizuno Y, Kazuyama Y, Hara T
  • Journal Title: Pediatr Infect Dis J 27(11) Pages: 1027-1030
  • Peer Reviewed
• [Journal Article] An effective scoring system of chest CT for assessing the clinical status of neonatal bfonchopulmonary dysplasia (2008)
  • Author(s): Ochiai M, Hikino S, Yabuuchi H, Nakayama H, Sato K, Ohga S, Hara T
  • Journal Title: J Pediatr 152(1) Pages: 90-95
  • Peer Reviewed
• [Journal Article] Prospective multicenter trial comparing repeated immunosuppressive therapy with stem cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia (2008)
  • Author(s): Kosaka Y, Yagasaki H, Sano K, Kobayashi R, Ayukawa H, Kaneko T, Yabe H, Tsuchida M, Mugishima H, Ohara A, Morimoto A, Otsuka Y, Ohga S, Bessho F, Nakahata T, Tsukimoto I, Kojima S
  • Journal Title: Blood 111(3) Pages: 1054-1059
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide-induced monocytic cell death for the diagnosis of mild neonatal-onset multisystem inflammatory disease (2008)
  • Author(s): Takada H, Ishimura M, Inada H, Ohga S, Kusuhara K, Moroi Y, Fume M, Hara T
  • Journal Title: J Pediatr 152(6) Pages: 885-887
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor-II : a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors (2008)
  • Author(s): Nagatomo T, Muta K, Ohga S, Ochiai M, Ohshima K, Hara T
  • Journal Title: Exp Hematol 36(4) Pages: 401-411
  • Peer Reviewed
• [Journal Article] Head circumference and long-term outcome in small-for gestational age infants (2008)
  • Author(s): Ochiai M, Nakayama H, Sato K, Iida K, Hikino S, Ohga S, Tsukimori K, Wake N, Masumoto K, Taguchi T, Hara T
  • Journal Title: J Perinat Med 36(4) Pages: 341-347
  • Peer Reviewed
• [Journal Article] Thromboembolic complications in splenectomized patients with dominantly inherited beta-thalassemia (2008)
  • Author(s): Ohga S, Ideguchi H, Kato J, Ishimura M, Takada H, Harada N, Kawanaka H, Hattori Y, Kang D, Hamasaki N, Hara T
  • Journal Title: Acta Haematol-Basel 120(1) Pages: 31-35
  • Peer Reviewed
• [Journal Article] Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan (2008)
  • Author(s): Sato E, Ohga S, Kuroda H, Yoshiba F, Nishimura M, Nagasawa M, Inoue M, KawaK
  • Journal Title: Am J Hematol 83(9) Pages: 721-727
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus associated encephalomyelitis : Intrathecal reactivation of the virus in an immunocompetent child (2008)
  • Author(s): Sanefuji M, Ohga S, Kira R, Nomura A, Torisu H, Takada H, Kusuhara K, Hara T
  • Journal Title: J Child Neurol 50(3) Pages: 723-726
  • Peer Reviewed
• [Journal Article] Early-onset sarcoidosis mimicking refractory cutaneous histiocytosis (2008)
  • Author(s): Ohga S, Ichino K, Urabe K, Ishimura M, Takada H, Nishikomori R, Fume M, Hara T
  • Journal Title: Pediatr Blood Cancer 50(3) Pages: 723-726
  • Peer Reviewed
• [Journal Article] Sjogren's syndrome-associated meningoencephalomyelitis : cerebrospinal fluid cytokineslevels and therapeutic utility of tacrolimus (2008)
  • Author(s): Hoshina T, Yamaguchi Y, Ohga S, Kira R, Ishimura M, Takada H, Tanaka T, Hara T
  • Journal Title: J Neurol Sci 267(1-2) Pages: 182-186
  • Peer Reviewed
• [Presentation] Clinical outcomes of stem cell transplantation for childhood hemophagocytic lymphohistiocytosis (HLH/HPS) in Japan (2009)
  • Author(s): Ohga S, Kudo K, Morimoto A, Honjo S, Osugi Y, Inoue M, Tabuchi K, Suzuki N, Ishida Y, Kawa K, Imashuku S, Hara T, Kato S, Ishii E
  • Organizer: The 4^<th> JSPS-NRCT Hematology Workshop by Asian CORE Program
  • Place of Presentation: Bangkok Thailand
  • Year and Date: 2009-02-20
• [Presentation] Hematopoietic stem cell transplantation for familial hemophagocytic lymphohistiocytosis or Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in Japan (2008)
  • Author(s): Ohga S, Kudo K, Osugi Y, Sawada A, Tabuchi K, Suzuki N, Morimoto A, Ishida Y, Kato S, Ishii E
  • Organizer: The 24th Annual Meeting of Histiocyte Society
  • Place of Presentation: Berlin, Germany
  • Year and Date: 20081001-20081003
• [Presentation] Nationwide survey of single system single site (SS-s)Langerhans cell histiocytosis in Japan. (2008)
  • Author(s): Morimoto A, Ishii E, Ohea S, Kudou K, Ishida Y, Suzuki N
  • Organizer: The 24th Annual Meeting of Histiocyte Society
  • Place of Presentation: Berlin, Germany
  • Year and Date: 20081001-20081003
• [Presentation] Pathophysiology and treatment of Diamond-Blackfan anemia (2008)
  • Author(s): Ohga S
  • Organizer: The 3^<rd> JSPS-NRCT Hematology Workshop by Asian CORE Program
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 20080627-20080628