• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Analysis of molecular mechanism of antibody deficiencies and development of their therapeutics

Research Project

Project/Area Number 08670872
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNagoya University

Principal Investigator

TSUGE Ikuya  Nagoya University Pediatrics School of Medicine Research associate, 医学部, 助手 (00231431)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsantibody deficiency / severe combined immunodeficiency / bone marrow transplantation / 抗体産生不全症
Research Abstract

Since 1981, a total of ten HLA-matched or -partially matched bone marrow transplantations (BMT) were performed on patients with severe combined immunodeficiency (SCID) at the Department of Pediatrics of the Nagoya University Hospital. Nine of these patients survived, but two X-linked SCID (X-SCID) patients showed a persistent deficiency of antibody production, despite their normal T cell functions and the existence of a normal number of B cells. Bone marrow condioning was not performed in the BMT for SCID and normal to elevated number of B cells exists before BMT in case of X-SCID patients. Therefore, it can be speculated that a chimeric state of donor-derived T cells and recipient-derived B cells persists for a long period. As antibody production were consistently recovered after HLA-matched BMT in this situation, persistent deficiency of antibody production seems not to be due to intrinsically defective B cells from patients, but to be due to defects of T cell- B cell cooperation. To evaluate this hypothesis and to get a clue to clarify the pathogenesis of primary antibody deficiency diseases, we analyzed the chimeric states and the in vitro antibody production of these patients. The results demonstrated that patient-derived B cells persists for a long period after BMT for X-SCID,that the degree of defective gc did not affect the persistent defects of antibody production, and that B cells ; seemed to be in a state similar to an antigen-unresponsiveness. Further study in necessary to clarify the mechanism of the unresponsiveness. I will continue to study the pathogenesis of antibody deficiencies to develop better methods for diagnosis and treatments.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Kuzushima, K., et al: "Establishment of anti-Epstein-Barr virus(EBV)cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection." Clin Exp Immunol. 103. 192-198 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hashimoto, S., et al: "Identification of Bruton's tyrosine kinase(BtK)gene mutations and characterization of the derived proteins in 35X-linked agammaglobulinemia families:a nationwide study of BtK deficiency in Japan." Bloodl. 88. 561-573 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuge, I., et al: "Interleukin-2 receptor γ-chain mutations in severe combined immunodeficiency with B lymphocytes." Eur j Ped. 155. 1018-1024 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morita, M., et al: "Calcification in the basal ganglia of three children with chronic active Epstein-Barr virus infection." Neurology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuge, I., et al: "Scuccessful PCR-based diagnosis of fungal meningitis in a patient with chronic granulomatous disease." Acta Ped Jpn. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuge, I., et al: "Necrotizing Toxoplasmic Encephalitis in a Child with the X-linked Hyper-IgM Syndrome." Eur J Ped. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuzushima, K., Yamamoto, M., Kimura, H., Ando, Y., Kudo, T., Tsuge, I., Morishima, T.: "Establishment of anti-Epstein-Barr virus (EBV) cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection" Clin.Exp.Immunol.103. 192-198 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hashimoto, S., Tsukada, S., Matsushita, M., Miyawaki, T., Niida, Y., Yachie, A., Kobayashi, S., Iwata, T., Hayakawa, H., Matsuoka, H., Tsuge, I., Yamadori, T., Kunikata, T., Arai, S., Yoshizaki, K., Taniguchi, N., Kishimoto, T.: "Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families : a nation wide study of Btk deficiency in Japan" Blood. 88. 561-73 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuge, I,Matsuoka, H., Abe, H., Kamachi, Y., Torii, S.: "Interleukin-2 receptor g-chain mutations in severe combined immunodeficiency with B lymphocytes" Eur.J.Pediatr.155. 1018-1024 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Morita, M., Tsuge, I., Matsuoka, H., Ito, Y., Itosu, T., Yamamoto, M., Morishima, T.: "Calcification in the basal ganglia of three children with chronic active Epstein-Barr virus infection" Neurology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuge, I,Makimura, K., Natsume, J., Kubota, T., Hasegawa, S., Kawabe, T., Nakashima, S., Aso, K., Negoro, T., Watanabe, K.: "Scuccessful PCR-based diagnosis of fungal meningitis in a patient with chronic granulomatous disease" Acta.Ped.Jpn.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tsuge, I., Matsuoka, H., Nakagawa, A., Kamachi, Y., Aso, A., Negoro, T., Ito, M., Torii, S., and Watanabe, K.: "Necrotizing Toxoplasmic Encephalitis in a Child with the X-linked Hyper-IgM Syndrome" Eur.J.Ped.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuzushima,K., et al.: "Establishment of anti-Epstein-Barr virus(EBV)cellular immunity by adoptive transfer of virus-specific cytotoxic T lymphocytes from an HLA-matched sibling to a patient with severe chronic active EBV infection." Clin Exp Immunol. 103. 192-198 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hashimoto,S., et al.: "Identification of Bruton's tyrosine kinase(Btk)gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan." Bloodl. 88. 561-573 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuge,I., et al.: "Interleukin-2 receptor γ-chain mutations in severe combined immunodeficiency with B Iymphocytes." Eur j Ped. 155. 1018-1024 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Morita,M., et al.: "Calcification in the basal ganglia of three children with chronic active Epstein-Barr virus infection." Neurology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuge,I., et al.: "Scuccessful PCR-based diagnosis of fungal meningitis in a patient with chronic granulomatous disease." Acta Ped Jpn. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuge,I., et al.: "Necrotizing Toxoplasmic Encephalitis in a Child with the X-linked Hyper-IgM Syndrome." Eur J Ped. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Hashimoto S,et al.: "Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families." Blood. 88. 561-573 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tsuge I,et al.: "Interleukin-2 receptor γ-chain mutations in severe combined immunodeficiency with Blymphocytes." Eur J Pediatr. 155. 1018-1024 (1996)

    • Related Report
      1996 Annual Research Report

URL: 

Published: 1996-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi