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Pitfalls in Neonatal Mass-screening for Cretinism - False hyperthyrotropinemia caused by human anti-mouse antibody (HAMA) of meternal origin

Research Project

Project/Area Number 10670699
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionAsahikawa Medical College

Principal Investigator

ITO Yoshiya (1999-2001)  Asahikawa Medical College, Pediatrics, Instructor, 医学部, 助手 (70241437)

矢野 公一 (1998)  旭川医科大学, 医学部, 講師 (60182383)

Co-Investigator(Kenkyū-buntansha) ISHII Takuma  Asahikawa Medical College, Pediatrics, Instructor, 医学部, 助手 (70312452)
蒔田 芳男  旭川医科大学, 医学部, 助手 (20271778)
伊藤 善也  旭川医科大学, 医学部, 助手 (70241437)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsNeonatal Mass-Screening / TSH / HAMA / Cretinism / Anti-Mouse Antibody / false hyperthyrotropinemia / 新生児マス・スクリーニング / 抗TSH抗体
Research Abstract

We had two cases with falsely positive results in neonatal screening for congenital hypothyroidism.The TSH activity in the sera from both infants and mothers corresponded to the peak of serum IgG in size-exclusion HPLC analysis. However, no anti-TSH autoantibody was detected in these sera. The TSH levels decreased when the sera were treated with protein A or immunoabsorbed with anti-human IgG serum. Furthermore, the high levels of serum TSH were abolished by using sheep, but not mouse, anti-human TSH antibody as a capture antibody. These results demonstrate that placental transfer of maternal IgG class human anti-mouse antibody (HAMA) results in falsely elevated TSH levels in newborn sera in sandwich immunoassays using mouse anti-TSH monoclonal antibody.
We studied another cause of falsely positive elevation of TSH. Two boys and their mother had high TSH value with normal thyroid function. Elevation of TSH value in the boys were gradually diminished, so that placentally transferred substance may cause false hyperthyrotropinemia. In the TSH profile of HPLC analysis, two peaks are detected from sera of their mother. One peak corresponded to TSH molecule and another one is just near the TSH peak. The binding of extracted IgG with TSH was 37.2 %. We concluded these boys with falsely elevated TSH had anti-TSH autoantibody, which were transferred from their mother through placenta.
In the last year we did nation-wide survey to explore the incidence of false hyperthyrotropinemia in neonatal screening for congenital hypothyroidism. In this survey 160 (from 130 to 234) patients were reported to have congenital hypothyroidism each year in these 10 years. But we have only 3 cases with falsely elevated TSH value. It is very difficult to get the precise information about the cases with false hyperthyrotropinemia from the central laboratories in each prefectures.

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] 矢野公一: "新生児マス・スクリーニングで発見された見かけ上の高TSH血症の母児例"ホルモンと臨床. 46. 105-110 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 矢野公一: "クレチン症マス・スクリーニングのPitfall母体の抗TSH抗体による高TSH血症"ホルモンと臨床. 47. 82-86 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 森山隆則: "母体由来のヒト抗マウス抗体(HAMA)による新生児の見かけ上の高TSH血症に関する研究"北海道大学医療技術短期大学部紀要. 13. 1-7 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yano K. et al.: "False hyperthyrotropinemia in infant and his mother discovered in neonatal mass-screening"Horumon to Rinsho. 46. 105-110 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yano K. et al.: "Pitfall in neonatal mass-screening for congenital hypothyroidism"Horumon to Rinsho. 46. 105-110 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Moriyama T. et al.: "Studies on false hyperthyrotropinemia caused by human anti-mouse antibody (HAMA) of maternal origin"Hokkaido Daigaku Iryou Gijutsu Tankidaigakubu Kiyou. 13. 1-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 矢野公一: "クレチン症マス・スクリーニングのPitfall -母体の抗TSH抗体による高TSH血症"ホルモンと臨床. 47(増刊号). 82-86 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 矢野公一: "新生児マス・スクリーニングで発見された見かけ上の高TSH血症の母児例" ホルモンと臨床. 46(増刊号). 105-110 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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