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

我们有两个病例假阳性结果在新生儿筛查先天性甲状腺功能减退。在大小排斥HPLC分析中，婴儿和母亲血清中TSH活性与血清IgG的峰值相对应。然而，在这些血清中未检测到抗tsh自身抗体。用蛋白A处理或用抗人IgG血清免疫吸收后血清TSH水平降低。此外，用绵羊而不是小鼠的抗人TSH抗体作为捕获抗体，可以消除血清中高水平的TSH。这些结果表明，在小鼠抗TSH单克隆抗体夹心免疫检测中，母体IgG类人抗小鼠抗体（HAMA）胎盘转移可导致新生儿血清中TSH水平虚高。我们研究了另一个导致TSH假阳性升高的原因。两个男孩和他们的母亲TSH值高，甲状腺功能正常。男孩的TSH值升高逐渐降低，因此胎盘转移的物质可能引起假的高甲状腺素血症。在HPLC分析的TSH谱中，在其母亲的血清中检测到两个峰。一个峰对应于TSH分子，另一个恰好在TSH峰附近。IgG与TSH的结合率为37.2%。我们得出结论，这些TSH错误升高的男孩有抗TSH自身抗体，该抗体是通过胎盘从母亲那里转移过来的。去年，我们在全国范围内进行了一项调查，探讨先天性甲状腺功能减退症新生儿筛查中假高甲状腺蛋白血症的发生率。在这10年中，每年报告有160例（从130例到234例）患者患有先天性甲状腺功能减退症。但我们仅有3例TSH值虚高。从各县的中心实验室获得假甲亢病例的准确信息是非常困难的。

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.