Specific Measurement of O-Linked Core 2 Sugar-Containing Isoforms of Hyperglycosylated Human Chorionic Gonadotropin by Antibody B152

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Abstract
There have been a significant number of reports on the clinical utility of measurement of 'hyperglycosylated' isoforms of the pregnancy hormone, human chorionic gonadotropin (hCG). Although there are a variety of hCG isoforms which can be termed 'hyperglycosylated', the measurements were all made using a unique antibody designated B152. This antibody was raised using a choriocarcinoma-derived form of hCG, which was hyperglycosylated with N- and O-glycans and was also 100% 'nicked' hCG. Antibody B152 was recently mapped to a linear epitope around a single O-glycan on the beta-subunit of hCG at residue number 132. Thus, the antibody can only measure isoforms of hCG that possess a core 2 type of branched O-glycan on this portion of the hCG beta-subunit. Isoforms that are hyperglycosylated in the hCG alpha-subunit or only on the N-glycans of hCGbeta will not be recognized by antibody B152. Apparently, measurements of these core 2 hCG isoforms have important clinical application in early pregnancy during which they are the predominant isoform of hCG until the 6th week of gestation. The secretory pattern of these isoforms can be used to predict the health status of the pregnancy in fertility clinics. Moreover, the measurements of these core 2 hCG isoforms are more useful than standard hCG for the prediction of Down syndrome pregnancies. The core 2 isoforms are also of important use in cancer diagnosis and monitoring since their concentration appears to correlate with malignancy.

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