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

本文报道了2例新生儿先天性甲状腺功能低下症筛查假阳性的病例，其新生儿及母亲血清中TSH活性均与体积排阻HPLC法测定的血清IgG峰相对应。然而，在这些血清中未检测到抗TSH自身抗体。当血清用蛋白A处理或用抗人IgG血清免疫吸收时，TSH水平下降。此外，高水平的血清TSH被取消，而不是使用羊，抗人TSH抗体作为捕获抗体。这些结果表明，母体IgG类人抗鼠抗体（HAMA）的胎盘转移导致新生儿血清中TSH水平的假阳性升高。两个男孩和他们的母亲有高TSH值与甲状腺功能正常。男孩TSH值升高逐渐减弱，胎盘转移物质可引起假性高促甲状腺素血症。在HPLC分析的TSH图谱中，从其母亲的血清中检测到两个峰。一个峰对应于TSH分子，另一个峰刚好靠近TSH峰。提取的IgG与TSH的结合率为37.2%。我们认为这些TSH假性升高的男孩有抗TSH自身抗体，这些抗体是通过胎盘从母亲那里转移过来的。10年来每年报告先天性甲状腺功能减退症160例（130 ~ 234例）。但我们只有3例TSH值假性升高。从各道府县中心实验室获得假性高促甲状腺素血症病例的准确信息非常困难。

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.