Loss of Hep Par 1 immunoreactivity in the livers of patients with carbamoyl phosphate synthetase 1 deficiency
Loss of Hep Par 1 immunoreactivity in the livers of patients with carbamoyl phosphate synthetase 1 deficiency
复制标题
氨基甲酰磷酸合成酶 1 缺乏症患者肝脏中 Hep Par 1 免疫反应性丧失
作者：
Yamaguchi M;Kataoka TR;Shibayama T;Fukuda A;Nakazawa A;Minamiguchi S;Sakurai T,Miyagawa-Hayashino A;Yorifuji T;Kasahara M;Uemoto S;Haga H
肝细胞石蜡1（Hep Par 1）抗体被广泛用作肝细胞标志物，识别氨甲酰磷酸合成酶1（CPS 1），这是尿素循环的重要组分。CPS1基因中存在各种错义、无义和移码突变。在纯合型CPS1缺乏症（CPS1D）的新生儿患者中，尿素循环缺陷导致的严重高氨血症可能是致命的，尽管肝移植可完全治愈CPS1D。我们对10例CPS1D肝移植患者的移植肝脏进行了Hep Par 1免疫染色。7例肝细胞中Hep Par 1阴性，另外3例显示正常弥漫性颗粒状胞质染色。正如预期的那样，所有三名Hep Par 1阳性患者至少有一个错义突变，所有四名仅具有无义或移码突变的患者都是Hep Par 1阴性。其他三名患者意外地对Hep Par 1呈阴性，尽管每个人都有一个错义突变。这些结果表明，CPS 1D可能与由于蛋白质产量损失而导致的Hep Par 1反应性丧失、导致蛋白质产物流产的一个氨基酸取代或两者兼而有之有关。Hep Par 1免疫组化可作为一种简便的方法来确认CPS 1D。
The hepatocyte paraffin 1 (Hep Par 1) antibody is widely used as a hepatocyte marker, recognizing carbamoyl phosphate synthetase 1 (CPS1), an essential component of the urea cycle. Various missense, nonsense, and frameshift mutations occur in theCPS1gene. In neonatal patients with homozygous CPS1 deficiency (CPS1D), urea cycle defects with resulting severe hyperammonemia can be fatal, though liver transplantation provides a complete cure for CPS1D. We performed Hep Par 1 immunostaining in the explanted livers of 10 liver transplant patients with CPS1D. Seven were negative for Hep Par 1 in the hepatocytes and the other three showed normal diffuse granular cytoplasmic staining. As expected, all three Hep Par 1‐positive patients had at least one missense mutation, and all four patients who had only nonsense or frameshift mutations were Hep Par 1‐negative. The other three patients were unexpectedly negative for Hep Par 1, even though each had one missense mutation. These results suggest that CPS1D can be related to the loss of Hep Par 1 reactivity due to the loss of protein production, a one amino acid substitution resulting in an abortive protein product, or both. Hep Par 1 immunohistochemistry can be used as a simple method to confirm CPS1D.