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Analysis of the pathogenesis of acute GVHD like illness caused by HHV-6 infection after hematopoietic stem cell transplantation

Research Project

Project/Area Number 14570740
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionFujita Health University

Principal Investigator

YOSHIKAWA Tetsushi  Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (80288472)

Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsHHV-6 / SCT / acute GVHD / cytokine / RNA / real-time PCR / 造血幹細胞移植 / サイトカイン / SCT / cytokines / RNA / HHV-7 / BMT / reactivation / skin rash
Research Abstract

Although it has been demonstrated that human herpesvirus 6 (HHV-6) infection occurs almost half of the hematopoietic stem cell transplant (HSCT) recipients, and might be associated with several clinical manifestations including acute graft versus host disease, mechanisms of viral reactivation remains unclear. To explore the mechanisms of HHV-6 reactivation in HSCT recipients, we sequentially monitored serum proinflamatory cytokines (IL-G, TNF-α, and IL-1β) levels and HHV-6 infection (viral isolation and serological assay) in the 24 pediatric patients after HSCT. Of the patients, 14 (58.3%) developed HHV-6 infection, and 9 (37.5%) developed HHV-6 viremia around 2 weeks (days 0, 14, 15, 14, 16, 15, 13, 21, and 22) after transplantation. The mean levels of three cytokines (IL-6, TNF-α, and IL-1β), which were measured at days 0, 7, 14, and 28 of post-transplant, were compared between patients with HHV-6 infection and those without HHV-6 infection. IL-6 levels were significantly higher in patients with HHV-6 infection than in those without HHV-6 infection at day 7 (54.8 vs 16.3 pg/ml; P=0.0272), 14 (44.2 vs 0.4 pg/ml; P=0.0002), and 28 (18.8 vs 4.4 pg/ml; P=0.0137). In addition, TNF-α level was significantly higher in patients with HHV-6 infection than in those without HHV-6 infection at day 14 (13.1 vs 3; P= 0.023). In other time points, there was no significant difference of mean IL-6 and TNF-α levels between. patients with HHV-6 infection and those without HHV-6 infection. Low level of IL-16 was detected in small number of serum samples, and there was no significant difference between patients with HHV-6 infection and those without HHN-6 infection. These results suggest that proinflamatory cytokines, in particular IL-6 and TNF-α, may play an important role in the pathogenesis of HHV-6 infection after HSCT, and may be a useful predictor for HHV-6 :infection.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (25 results)

All 2004 Other

All Journal Article (13 results) Publications (12 results)

  • [Journal Article] Rapid diagnosis of human herpesvirus 6 infection by a novel DNA amplification method-loop-mediated isothermal amplification.2004

    • Author(s)
      Ihira M, Yoshikawa T, Enomoto Y, et al.
    • Journal Title

      Journal of Clinical Microbiology 42

      Pages: 140-145

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Human herpesvirus 6 infection in hematopoietic stem cell transplant patients.2004

    • Author(s)
      Yoshikawa T
    • Journal Title

      British Journal of Haematology 124

      Pages: 421-432

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Monitoring of herpesviruses DNA in three cases of acute retinal necrosis by real-time PCR.2004

    • Author(s)
      Asano S, Yoshikawa T, Kimura H, et al.
    • Journal Title

      Journal of Clinical Virology 29

      Pages: 206-209

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Rapid diagnosis of human herpesvirus 7 infection by a novel DNA amplification method-loop-mediated isothermal amplification.2004

    • Author(s)
      Yoshikawa T, Ihira M, Akimoto S, et al.
    • Journal Title

      Journal of Clinical Microbiology 42

      Pages: 1348-1352

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Detection of aerosolized varicella-zoster virus DNA in patients with localized zoster.2004

    • Author(s)
      Suzuki K, Yoshikawa T, Tomitaka A, et al.
    • Journal Title

      Journal of Infectious Diseases 189

      Pages: 1009-1012

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Atypical clinical features of human herpesvirus-6 infection in a neonate.2004

    • Author(s)
      Yoshikawa T, Suzuki K, Umemura K, et al.
    • Journal Title

      Journal of Medical Virology 74

      Pages: 463-466

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Rapid diagnosis of human herpesvirus 6 infection by a novel DNA amplification method-loop-mediated isothermal amplification.2004

    • Author(s)
      Ihira M, Yoshikawa T, Enomoto Y, et al.
    • Journal Title

      J Clin Microbiol 42

      Pages: 140-145

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Human herpesvirus 6 infection in hematopoietic stem cell transplant patients.2004

    • Author(s)
      Yoshikawa T.
    • Journal Title

      Brit J Haematol 124

      Pages: 421-432

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Monitoring of herpesviruses DNA in three cases of acute retinal necrosis by real-time PCP.2004

    • Author(s)
      Asano S, Yoshikawa T, Kimura H, et al.
    • Journal Title

      J Clin Virol 29

      Pages: 206-209

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rapid diagnosis of human herpesvirus 7 infection by a novel DNA amplification method-loop-mediated isothermal amplification.2004

    • Author(s)
      Yoshikawa T, Ihira M, Akimoto S, et al.
    • Journal Title

      J Clin Microbiol 42

      Pages: 1348-1352

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Detection of aerosolized varicella-zoster virus DNA in patients with localized zoster.2004

    • Author(s)
      Suzuki K, Yoshikawa T, Tomitaka A, et al.
    • Journal Title

      J Infect Dis 189

      Pages: 1009-1012

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rapid detection of varicella-zoster virus infection by loop-mediated isothermal amplification method.2004

    • Author(s)
      Okamoto S, Yoshikawa T, Ihira M, et al.
    • Journal Title

      J Med Virol 74

      Pages: 677-682

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Atypical clinical features of human herpesvirus-6 infection in a neonate.2004

    • Author(s)
      Yoshikawa T, Suzuki K, Umemura K, et al.
    • Journal Title

      J Med Virol 74

      Pages: 463-466

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yoshikawa T et al.: "Evaluation of active human herpesvirus 6 infection by reverse transcription-PCR."Journal of Medical Virology. 70. 267-272 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshikawa T et al.: "Human herpesvirus 7 associated meningitis and optic neuritis in a patient after allogeneic stem cell transplantation."Journal of Medical Virology. 70. 440-443 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshikawa T et al.: "Human herpesvirus 6 infection of human epidermal cell line ; pathogenes is of skin manifestations."Journal of Medical Virology. 71. 62-68 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshikawa T et al.: "Rapid diagnosis of human herpesvirus 7 infection by a novel DNA amplification method-loop-mediated isothermal amplification."Journal of Clinical Microbiology. In press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Ihira M, Yoshikawa T et al.: "Variation of human herpesvirus 7 shedding in saliva : individual variation."Journal of Infectious Diseases. 188. 1352-1354 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawada J, Yoshikawa T et al.: "Systemic cytokine responses in patients with influenza-associated encephalopathy."Journal of Infectious Diseases. 188. 690-698 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshikawa T et al.: "Human herpesvirus 6 viremia in bone marrow transplant recipients : clinical features and risk factors"Journal of Infectious Diseases. 185. 847-853 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshikawa T et al.: "Fatal adult case with severe lymphocytopenia associated with reactivation of human herpesvirus 6"Journal of Medical Virology. 66. 82-85 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshikawa T et al.: "Latent infection of human herpesvirus 6 in astrocytoma cell line and alteration of cytokine synthesis"Journal of Medical Virology. 66. 497-505 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshikawa T: "Human herpesvirus 6 and 7 infections in transplantation"Pediatric Transplantation. 7. 11-17 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshikawa T et al.: "Human herpesvirus 7 associated meningitis and optic neuritis in a patient after allogeneic stem cell transplantation"Journal of Medical Virology. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshikawa T et al.: "Human herpesvirus 6 infection of human epidermal cell line ; pathogenesis of skin manifestations"Journal of Medical Virology. (In press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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