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

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 β-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 β-subunit. Isoforms that are hyperglycosylated in the hCG α-subunit or only on the N-glycans of hCGβ 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.

hCG and Hyperglycosylated hCG Carbohydrate Structure Corrected

“…The specificity of this antibody is for hyperglycosylated hCG [7,8]. As published, this antibody detects an O-linked oligosaccharide on hCG at Ser 132 and segments of ß-subunit and a-subunit peptide [21]. The specificity of the assay using antibody B152 is confirmed here.…”

Role of Pregnancy Associated Plasma Protein (PAPP-A) and Free Human Chorionic Gonadotropin (B-HCG) in Predicting Adverse Pregnancy Outcomes

“…Bunların yanında, birçok araştırmacı kötü gebelik sonuçlarını öngörmek için daha farklı maternal serum belirteçleri de kullanmışlardır. Bu araştırmacılar ikinci trimester bağlanmamış serum estriol seviyelerinin düşüklüğünün; intrauterin gelişme kısıtlılığı (IUGR), düşük amniyotik sıvı indeksi, gestasyonel yaş için küçük gebelik (SGA) ve fetal kayıp gibi komplikasyonlar ile artmış birlikteliğini bulmuşlardır (7)(8)(9)(10)(11) .…”

Determination of hyperglycosylated human chorionic gonadotropin produced by malignant gestational trophoblastic neoplasias and male germ cell tumors using a lectin-based immunoassay and surface plasmon resonance

“…The term hyperglycosylation as used for hCG is typically understood to mean enhanced branching into triantennary and unusual biantennary N-linked oligosaccharides, and a preponderance of the more complex Core 2, as opposed to Core 1, O-linked sugars, (Kobata 1988, Elliott et al 1997, Birken et al 2003. However, since the development of the only antibody which can specifically recognize forms of hyperglycosylated hCG which contain Core 2 O-linked sugars on the hCGβ COOH-terminal region (B152), the term hyperglycosylated is now frequently used to mean forms of hCG recognized by the particular antibody , Birken 2005.…”

“…Although only germ cell tumors, choriocarcinoma, invasive mole, and placental site trophoblastic tumors secrete the prodigious quantities of hormone traditionally required for structural determination of the oligosaccharide chains, hCG produced by transformed cells differs from pregnancy-derived hCG in its retention or exclusion on lectin affinity columns (Yoshimoto et al 1979, Mann & Karl 1983, Endo et al 1988, Sakai et al 1994, implying that perhaps all malignancy-derived hCG carries altered carbohydrate structures. There is evidence that the hyperglycosylated forms of hCG in pregnancy differ somewhat from those produced by various malignancies (Kovalevskaya et al 2002b, Birken 2005.…”