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Investigation of Systemic and Local Immune-mechanism for Maintenance of Human Pregnancy

Research Project

Project/Area Number 04454425
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionKeio University

Principal Investigator

MAKINO Tsunehisa  keio University, School of Medicine, Assistant Professor, 医学部, 講師 (30085758)

Co-Investigator(Kenkyū-buntansha) 細川 知俊  慶應義塾大学, 医学部, 助手 (10238751)
染谷 健一  慶應義塾大学, 医学部, 助手 (90236159)
OZAWA Nobuaki  Keio University, School of Medicine, Clinical fellow, 医学部, 助手 (70224219)
MATSUBAYASHI Hidehiko  Keio University, School of Medicine, Clininal fellow, 医学部, 助手 (40219465)
MARUYAMA Tetsuo  Keio University, School of Medicine, Clinical fellow, 医学部, 助手 (10209702)
IWASAKI Ken-ichi  Keio University, School of Medicine, Clininal fellow, 医学部, 助手 (00203365)
SUGI Toshitaka  Keio University, School of Medicine, Clinical fellow, 医学部, 助手 (70196707)
豊島 究  慶應義塾大学, 医学部, 助手 (00197964)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1993: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1992: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsHabitual abortion / Immunotherapy / Flow cytometry / Flow cytometric crossmatch / Activated T cell / Natulal killer cell / Blocking antibody / Decidua / 反復流産 / 不育症 / 全身性免疫 / 局所免疫 / 先天性子宮奇形
Research Abstract

First 1,520 couples with a history of recurrent spontaneous abortion were registered, then possible etiologic factors of the reproductive wastage were screened through comprehensive clinical examinations. Among these patienats, 214 congenial uterine malfomations, 106 chromosomal abnormalities in either husbands or wives, 24 antiphospholipid syndromes were detected. Other 482 couples were then the subjects whether they have any immunologic abnormalities in terms of maintenance of pregnancy.
Immunotherapy was performed in 473 female partners using paternal lymphocytes, resulting 77.7% of successful rate of maintenance of pregnancy. Mixed lymphocyte reaction (MLR) was significantly (p<0.001) inhibited after immunotherapy. The mean inhibition rate was 50.2%, indicating the MLR blocking antibodies were induced. It was also suggested that anti-idiotypic antibodies were gererated by immunotherapy. The percentage of cytotoxic T cell was significantly decreased (p<0.05) and that of suppressor T … More cell was significantly increased (p<0.01) after immunization, suggesting that a cell-mediated immune response was induced by immunotherapy. Two-color T cell flow cytometric crossmatch (T-FCXM) which can detect maternal IgG antibodies against paternal T lymphocytes predicts subsequent pregnancy outcome in patients undergoing immunotherapy. Anti-fetal lymphocyte antibodies were detected in only limited cases of immunized patients, suggesting that this antibody is not essential for the maintenance of pregnancy.
Flow cytometry was also used to characterize immune cell populations in the decidua to demonstrate how the proportions of immunocompetent cell populations at the feto-maternal interface are influenced by the presence and state of a feto-placental allograft. The percentage of decidual CD3^+/HLA DR^+ cells, which are characteristic of activated T cells, was significantly higher in spontaneous abortion than in normal pregnancy (p<0.05), suggesting that on/off-switching of activation of decidual T cells may be associated with maintenance of gestation.
All these studies summarized that multiple pathways of both systemic and local immune-system are essentical for the successful course of human pregnancy. Less

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Nobuaki Ozawa: "β_2-GPI-Dependent and Independent Binding of Anticardiolipin Antibodies in Patients with Recurrent Spontaneous Abortions" Journal of Clinical Laboratory Analysis. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ken-ichi Iwasaki: "Detection of Anti-lymphocyte Antibodies against Fetal Lymphocytes by Flow Cytometric Crossmatch during Human Pregnancy" Journal of Clinical Laboratory Analysis. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nobuaki Ozawa: "beta2-GPI-Dependent and Independent Binding of Anticardiolipin in Patients with Recurrent Spontaneous Abortions" Journal of Clinical Laboratory Analysis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ken-ichi Iwasaki: "Detection of Anti-lymphocyte Antibodies against Fetal Lymphocytes by Flow Cytometric Crossmatch during Human Pregnancy." Journal of Clinical Laboratory Analysis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nobuaki Ozawa: "b_2-GPI-Dependent and Independent Binding of Anticardialipin Antibodies in Patients with Recurrent 〓pontanpons Abortions" Journal of Clinical Laboratory Analysis. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Ken-ichi Iwasaki: "Detection of Anti-Iymphocyte Antibodies against Fetal Lymphocytes by Flow Cytometric Crossmatch during Human Pregnancy" Journal of Clinical Laboratory Analysis. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Makino: "Incidence of congenital uterine anomalies in repeated reproductive wastage and prognosis for pregnancy after metroplasty" International Journal of Fertility. 37. 167-170 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Makino: "Surrey of 1120 Japanese women with a history of recurrent spoutaneous abortions" European Journal of Obstetrics & Gynecology and Reproductive Biology. 44. 123-130 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 牧野 恒久: "抗リン脂質抗体" 臨床婦人科産科. 46. 1015-1016 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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