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ELUCIDATION OF PATHOGENETIC MECAHNISMS FOR SEVERE CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION SYNDROME

Research Project

Project/Area Number 12670720
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

OKANO Motohiko  Hokkaido Univ., Hospital., Lecturer, 医学部・附属病院, 講師 (50261300)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsEpstein-Barr virus / Infection / Active / Chronic
Research Abstract

Severe chronic active Epstein-Barr virus (EBV) infection syndrome (SCAEBV) is characterized by persistent or recurrent fever, lymph adenopathy, and hepatosplenomegaly. Laboratory data shows the tendency of pancytopenia and polyclonal gammopathy. Antibody titers against EBV replicating antigens such as viral capsid antigen (VCA) and early antigens (EA) are generally shown to be extremely high, and affected tissues are positive for EBV genome. Furthermore, patients with SCAEBV have very poor prognosis particularly owing to the development of EBV-positive T cell malignancies. A head investigator studied whether EBV and adenovirus type II (ADVII) coinfections occur in these patients by in vitro experiment because both EBV and ADVII were often identified from their tissue materials.
Five patients with SCAEBV were studied. All patients had antibodies against ADVII. Two cases showed increased numbers of both CD8-DR positive cells, two both CD4-DR positive cells, one both CD20-CD23 positive cel … More ls in their circulation, respectively. All these activated cells were positive for EBV genome. Two of them were positive for ADVII genome, as well. Following exogenous infection by either EBV or ADVII, no increased genome positive T cells were significantly demonstrated. No continuous lymphoblastoid cell lines were established either spontaneously from the patients because cytopathic effects (CPE) occurred remarkably. Notably, low interferongamma production was observed in all cultures.
These results suggested activated EBV infection underlain associated with defect of immunosurveillance in patients with SCAEBV. Although no absolute conclusion was evidenced, CPE shown in cultures highly indicated the presence of some lymphotropic viruses including ADVII. Additionally, some heterogeneity was observed in subpopulation regarding the activated EBV infected cells, which may contribute to the development of disease. The degree of severity and the time of disease process are possibly important to clarify the pathogenetic mechanisms in patients with SCAEBV. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (65 results)

All Other

All Publications (65 results)

  • [Publications] Okano M: "A review of Epstein-Barr virus infection in patients with immunodeficiency"Amer J Med Sci. 319・6. 392-396 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 岡野素彦: "原発性免疫不全症とは何か"小児内科. 32・11. 1949-1956 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Haematological associations of Epstein-Barr virus infection"Bailliere's Clin Haematol. 13・2. 199-214 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada M: "Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells"J Immunol. 165・2. 1119-1122 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I: "Platelet-specific hemophagocytosis in a patient with juvenile dermatomyositis"Acta Pediatr. 89・5. 617-617 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tateishi U: "High-resolution CT findings of macrophage activation syndrome : a case report"Pediatr Radiol. 30・10. 699-701 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawamura N: "Improved dysgammaglobulinemia in congenital rubella syndrome after immunoglobulin therapy : correlation with CD154 expression"Eur J Paediatr. 159・10. 764-766 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I: "KL-6 is a potential marker for interstitial lung disease associated with juvenile dermatomyositis"J Pediatr. 138・2. 274-276 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I: "Elevated serum levels of soluble interleukin-2 receptor in juvenile dermatomyositis"Pediatr Intl. 43・1. 109-111 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I: "Anti-alpha-fodrin autoantibody in an early diagnostic marker for childhood primary Sjogren's syndrome"J Rheumatol. 28・2. 363-365 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada M: "Combined immunodeficiency, chromosomal instability, and postnatal growth deficiency in a Japanese girl"Amer J Med Genet. 100・1. 9-12 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I: "A long-term survivor with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome(IPEX)"N Engl J Med. 345・13. 999-1000 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I: "Novel mutations of FOXP3 in two Japanese patients with immnune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome(IPEX:)"J Med Genet. 38・12. 874-876 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Burkitt's lymphoma to chronic active Epstein-Barr virus(EBV) infection : an expanding spectrum of EBV-associated diseases"Pediatr Hematol Oncol. 18・7. 427-442 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Epstein-Barr virus in patients with immunodeficiency disorders"Biomed Pharmacother. 55・7. 353-361 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Overview and problematic staudpointsu of severe chronic active Epstein-Barr virus infection syndrome"Crit Rev Hematol/Oncol. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 岡野素彦: "ウイルス感染における免疫応答と検査-EBウイルス感染症を中心に-"臨床検査. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 岡野素彦: "今日の小児治療指針(第13版)「原発性免疫不全症」"医学書院(印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano MA: "A review of Epstein-Barr virus infection in patients with immunodeficiency"Amer J Med Sci. 319. 392-396 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M, et al.: "Primary immunodeficiency diseases"Shoni Naika. 32(Japanese). 1949-1956 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Haematological associations of Epstein-Barr virus infection."Bailliere's Clin Haematol. 13. 199-214 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada M, et al.: "Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells."J Immunol. 165. 1119-1122 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I, et al.: "Platelet-specific hemophagocytosis in a patient with juvenile dennatomyositis."Acta Pediatr. 89. 617-619 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tateishi U, et al.: "High-resolution CT findings of macrophage activation syndrome: a case report."Pediatr Radiol. 30. 699-701 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawamura N, et al.: "Improved dysgammaglobulinemia in cogenital rubella syndrome after immunoglobulin therapy: correlation with CD154 expression."Eur J Paediatr. 159. 764-766 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I, et al.: "KL-6 is a potential marker for interstitial lung disease associated with juvenile dermatomyositis"J Pediatr. 138. 274-276 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I, et al.: "Elevated serum levels of soluble interleukin-2 receptor in juvenile dermatomyositis."Pediatr Intl. 43. 109-111 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I, et al.: "Anti-alpha-fodrin autoantibody in an early diagnostic marker for childhood primary Sjogren's syndrome."J Rheumatol. 28. 363-365 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada M, et al.: "Combined immunodeficiency, chromosomal instability, and postnatal growth deficiency in a Japanese girl."Amer J Med Genet. 100. 9-12 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I, et al.: "A long-term survivor with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)."N Engl J Med. 345. 999-1000 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi I, et al.: "Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)."J Med Genet. 38. 874-876 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "From Burkitt's lymphoma to chronic active Epstein-Barr virus (EBV) infection: an expanding spectrum of EBV-associated diseases."Pediatr Hematol Oncol. 18. 427-442 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Epstein-Barr virus in patients with immunodeficiency disorders."Biomed Pharmacother. 55. 353-361 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Overview and problematic standpoints of severe chronic active Epstein-Barr virus infection syndrome."Crit Rev Hematol/Oncol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Immunological response and diagnostic approaches for Epstein-Barr virus infection (Japanese)."Rinsho Kensa. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "Primary immunodeficencies"Today's therapy in Pediatrics (13th ed), (in press) (Japanese).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okano M: "A review of Epstein-Barr virus infection in patients with immunodeficiency"Amer J Med Sci. 319・6. 392-396 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 岡野素彦: "原発性免疫不全症とは何か"小児内科. 32・11. 1949-1956 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okano M: "Haematological associations of Epstein-Barr virus infection"Bailliere's Clin Haematol. 13・2. 199-214 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada M: "Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells"J Immunol. 165・2. 1119-1122 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi I: "Platelet-specific hemophagocytosis in a patient with juvenile dermatomyositis"Acta Pediatr. 89・5. 617-619 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tateishi U: "High-resolution CT findings of macrophage activation syndrome : a case report"Pediatr Radiol. 30・10. 699-701 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawamura N: "Improved dysgammaglobulinemia in congenital rubella syndrome after immunoglobulin therapy : correlation with CD154 expression"Eur J Paediatr. 159・10. 764-766 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi I: "KL-6 is a potential marker for interstitial lung disease associated with juvenile dermatomyositis"J Pediatr. 138・2. 274-276 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi I: "Elevated serum levels of soluble interleukin-2 receptor in juvenile dermatomyositis"Pediatr Intl. 43・1. 109-111 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi I: "Anti-alpha-fodrin autoantibody in an early diagnostic marker for childhood primary Sjogren's syndrome"J Rheumatol. 28・2. 363-365 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada M: "Combined immunodeficiency, chromosomal instability, and postnatal growth deficiency in a Japanese girl"Amer J Med Genet. 100・1. 9-12 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi I: "A long-term survivor with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome(IPEX)"N Engl J Med. 345・13. 999-1000 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi I: "Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome(IPEX)"J Med Genet. 38・12. 874-876 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okano M: "Burkitt's lymphoma to chronic active Epstein-Barr virus(EBV) infection : an expanding spectrum of EBV-associated diseases"Pediatr Hematol Oncol. 18・7. 427-442 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okano M: "Epstein-Barr virus in patients with immunodeficiency disorders"Biomed Pharmacother. 55・7. 353-361 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Okano M: "Overview and problematic standpoints of severe chronic active Epstein-Barr virus infection syndrome"Crit Rev Hematol/Oncol. 印刷中.

    • Related Report
      2001 Annual Research Report
  • [Publications] 岡野素彦: "ウイルス感染における免疫応答と検査-EBウイルス感染症を中心に-"臨床検査. 印刷中.

    • Related Report
      2001 Annual Research Report
  • [Publications] 岡野素彦: "今日の小児治療指針(第13版)「原発性免疫不全症」"医学書院(印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] Okano M: "A review of Epstein-Barr virus infection in patients with immunodeficiency"Amer J Med Sci. 319・6. 392-396 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 岡野素彦: "原発性免疫不全症とは何か"小児内科. 32・11. 1949-1956 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okano M: "Haematological associations of Epstein-Barr virus infection"Bailliere's Clin Haematol. 13・2. 199-214 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamada M: "Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells"J Immunol. 165. 1119-1122 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi I: "Platelet-specific hemophagocytosis in a patient with juvenile dermatomyositis"Acta Pediatr. 89. 617-619 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tateishi U: "High-resolution CT findings of macrophage activation syndrome : a case report"Pediatr Radiol. 30. 699-701 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawamura N: "Improved dysgammaglobulinemia in congenital rubella syndrome after immunoglobulin therapy : correlation with CD154 expression"Eur J Paediatr. 159. 764-766 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi I: "KL-6 is a potential marker for interstitial lung disease associated with juvenile dermatomyositis"J Pediatr. 138・2. 274-276 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi I: "Elevated serum levels of soluble interleukin-2 receptor in juvenile dermatomyositis"Pediatr Intl. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi I: "Anti-alpha-fodrin autoantibody in an early diagnostic marker for childhood primary Sjogren's syndrome"J Rheumatol. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamada M: "Combined immunodeficiency, chromosomal instability, and postnatal growth deficiency in a Japanese girl"Amer J Med Genet. (印刷中).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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