Hyperglycosylated HCG expression in pregnancy: Cellular origin and clinical applications
Hyperglycosylated HCG expression in pregnancy: Cellular origin and clinical applications
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DOI：
10.1016/j.mce.2006.02.021
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发表时间：
2007-01-02
影响因子：
4.1
通讯作者：
O'Connor, J. F.
中科院分区：
文献类型：
--
作者：
Kovalevskaya, G.;Kakuma, T.;O'Connor, J. F.
利用单克隆抗体（b152）特异性针对绒毛膜癌衍生的hCG上发现的碳水化合物表位，发现在妊娠早期表达类似的hCG同种异构体。这种形式与妊娠后期hCG的碳水化合物部分不同。在整个妊娠期间对这两种hCG异构体进行分析使用了两种IRMA: B152-B207（“高糖化hCG”特异性检测）和B109-B108（一种用于WHO hCG参考制剂中标准完整hCG异构体的IRMA）。两项试验均采用WHO hCG标准。数值以hCG异构体浓度之比（B152/B109之比）表示。妊娠早期尿b152 hCG浓度正常妊娠（NP）明显高于妊娠早期损失（EPL）。早期和晚期妊娠的匹配血清-尿液样本显示，与晚期妊娠相比，b152 hCG形式在早期妊娠的血清和尿液中都占主导地位。b152 hCG （HhCG）形式的比例在尿液中高于匹配的血清。正常妊娠胚胎移植后第5天和第20天的B152/B109比与体外受精患者尿液中的EPL有显著差异。在自然流产（SA）中，NP组b109 hCG水平高于SA组。然而，B152/B109比值随着胎龄的下降，SA比NP更快，这可能表明SA与EPL的损失机制不同。通过细胞滋养层细胞（CTBs）和合胞滋养层细胞（STBs）的细胞培养基测定，确定了不同hCG糖型的细胞来源。分离的CTBs主要表达HhCG。表达水平在妊娠早期最高。STBs是糖基化程度较低的b109 hCG异构体的来源。分析妊娠早期hCG糖型可以区分妊娠失败和正常妊娠。由于B152检测不能有效区分完整HhCG和游离HhCG (HhCG β)，因此开发了一种新的HhCG β检测方法。该试验识别由CTBs产生的HhCG β。我们假设HhCG β的测量可能在唐氏综合症和其他妊娠疾病以及某些类型的癌症的筛查中有潜在的用途。2006爱思唯尔爱尔兰有限公司版权所有。
Employing a monoclonal antibody (B 152) specific for a carbohydrate epitope found on a choriocarcinoma derived hCG, it was discovered that a similar hCG isoform is expressed during early pregnancy. This form differs from later pregnancy hCG in carbohydrate moieties. Profiling of these two hCG isoforms throughout pregnancy utilized two IRMA's: B152-B207 ("hyperglycosylated hCG"-specific assay) and B109-B108 (an IRMA for standard intact hCG isoforms in the WHO hCG reference preparation). The WHO hCG standard was used in both assays. Values were presented as a ratio of hCG isoform concentrations (B152/B109 ratio). In early pregnancy urine concentrations of B 152 hCG were significantly higher in normal pregnancy (NP) compared to early pregnancy loss (EPL). Matched serum-urine samples from the first and third trimesters revealed that the B 152 hCG form is predominant in both serum and urine in the first trimester compared with the third trimester. The proportion of the B 152 hCG (HhCG) form is higher in urine than in matched serum. There was a significant difference in the B152/B109 ratio between days 5 and 20 from time of embryo transfer in normally developing pregnancy versus EPL in the urine of IVF patients. In spontaneous abortion (SA) the level of B 109 hCG remained higher in NP compared with SA. However, the B152/B109 ratio declined with gestational age faster in SA than in NP suggesting perhaps a different loss mechanism in SA versus EPL. The cellular origin of the different hCG glycoforms was identified by assay of cell media from cytotrophoblasts (CTBs) and syncytiotrophoblasts (STBs). Isolated CTBs expressed predominantly HhCG. The level of expression was the highest in the first trimester. STBs were the source of the less glycosylated B 109 hCG isoform. Analysis of hCG glycoforms during early pregnancy can distinguish pregnancies that will fail from those that will proceed normally. Since the B152 assay does not effectively discriminate between intact HhCG and free beta HhCG (HhCG beta), a new HhCG beta assay was developed. This assay recognizes the HhCG beta which is produced by CTBs. We hypothesize that the measurement of HhCG beta may have a potential use in screening for Down syndrome and perhaps other pregnancy disorders and certain types of cancer. (c) 2006 Elsevier Ireland Ltd. All rights reserved.