Hyperglycosylated hCG (invasive trophoblast antigen, ITA) a key antigen for early pregnancy detection

Cole, Laurence A.; Khanlian, Sarah A.; Sutton, Jaime M.; Davies, Suzy; Stephens, Nicole

doi:10.1016/s0009-9120(03)00108-5

Cited by 73 publications

(52 citation statements)

References 25 publications

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“…The current assay was also developed primarily for the latter purpose and therefore designed to detect intact and hyperglycosylated hCG as well as free hCG␤, which are the principal forms of hCG in blood during (early) pregnancy (5,42,43 ). However, it has recently been shown that many hCG assays have poorer sensitivity for hyperglycosylated hCG despite that fact that it is the major molecular form produced in the first weeks of pregnancy and therefore the key molecule in sensitive pregnancy detection (5,8 ). Furthermore, the variable detection of other hCG variants in addition to hyperglycosylated hCG has been shown to be a major cause of discordance among commercial assays (28,44 ), and not all tests are appropriate for use in applications other than for pregnancy testing.…”

Section: Discussionmentioning

confidence: 99%

“…The ability of hCG assays to also detect some irregular hCG molecular forms has become the subject of increasing discussion. Proper detection of hyperglycosylated hCG and the nicked forms of both hCG and hCG␤ is considered increasingly important because in early pregnancy and in trophoblastic disease these hCG variants may be the principal forms present in circulation (4,5 ).…”

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confidence: 99%

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Quantitative, Wide-Range, 5-Minute Point-of-Care Immunoassay for Total Human Chorionic Gonadotropin in Whole Blood

Lode

Rainaho²,

Pettersson

2004

Clinical Chemistry

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Background: Human chorionic gonadotropin (hCG) is among the most common analytes available for pointof-care immunotesting, with most assays currently based on simple manual assay devices. However, as the importance of good analytical performance of rapid assays is increasingly emphasized, more sophisticated immunoassay techniques are needed to meet the future challenges of rapid yet quantitative POC testing. Methods: We developed a simple, dry-reagent, all-inone immunoassay for the quantitative measurement of hCG in whole blood, plasma, or serum. The noncompetitive assay equally measures intact, nicked, and hyperglycosylated hCG as well as nonnicked and nicked hCG ␤-subunit with a rapid and simple procedure consisting of a 5-min, one-step incubation and, subsequent to washing, the measurement of time-resolved fluorescence directly from a wet well surface. Results: The assay had a detection limit (background ؉ 3 SD) of 0.4 IU/L hCG. The within-run CV was <15% down to 2 IU/L, and the assay was linear to 6000 IU/L. The within-and between-run CVs in heparinized whole blood and plasma were <10% throughout the measured range (4.0 -4400 IU/L). The mean (95% confidence interval) difference between whole blood and plasma was ؊42 (؊24 to ؊61)% without hematocrit correction and 6.5 (؊14 to 27)% with hematocrit correction (n ‫؍‬ 106). Regression analysis with the Diagnostic Products IMMULITE ® 2000 hCG method yielded the following: slope (SD), 1.02 (0.01); y-intercept (SD), ؊6 (10) IU/L; S yͦx ‫؍‬ 99 IU/L (n ‫؍‬ 124; range, 1.6 -4746 IU/L; r ‫؍‬ 0.995). Conclusions: Combined with the fully automated instrumentation, the 5-min, dry-reagent assay allows

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Quantitative, Wide-Range, 5-Minute Point-of-Care Immunoassay for Total Human Chorionic Gonadotropin in Whole Blood

Lode

Rainaho²,

Pettersson

2004

Clinical Chemistry

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“…LH was also determined using the Immulite 1000 assay. Hyperglycosylated hCG was determined as described previously [17,18]. Briefly, microtiter plates were coated with B152 antibody, an antibody against C5 hCG preparation [5,19].…”

Section: Methodsmentioning

confidence: 99%

“…The percentage hyperglycosylated hCG in USA hCG Reference Service urine was also calculated. Total hCG results (mIU/ml) were converted into ng/ml by dividing by 11 [17,18]. Hyperglycosylated hCG results (ng/ml) were divided by total hCG results (ng/ml) to yield the proportion hyperglycosylated hCG.…”

Section: Methodsmentioning

confidence: 99%

hCG and Hyperglycosylated hCG Carbohydrate Structure Corrected

Cole¹

2015

J Glycobiol

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Multiple articles have been published describing the N-linked and O-linked oligosaccharide structures of hCG. All, however, have used purified preparation from pregnancy urine and from choriocarcinoma patient urine. This has told the scientific community that pregnancy and choriocarcinoma hCG-related molecules contain Type 1 and Type 2 O-linked oligosaccharides and biantennary and triantennary N-linked oligosaccharide. Recent years have seen the demonstration of two completely independent hCG molecules, hCG and hyperglycosylated hCG. hCG is a pregnancy hormone made by syncytiotrophoblast cell. Hyperglycosylated hCG is a TGFß receptor binding autocrine produced by cytotrophoblast cells. The two independent share a common amino acid sequence and just vary in carbohydrate structure. Unfortunately, all the carbohydrate structure reports are on a mixture of hCG and hyperglycosylated hCG, as present in pregnancy and choriocarcinoma. This does not all anyone to clearly see the carbohydrate structural differences between the two molecules. Here we carefully examine the carbohydrate structural differences between hCG and hyperglycosylated hCG using the B152 hyperglycosylated hCG-specific immunoassay. It is shown that hCG has only Type 1 O-linked oligosaccharides, while hyperglycosylated hCG only has Type 2 O-linked oligosaccharides. Type of O-linked oligosaccharide structure completely distinguishes hCG and hyperglycosylated hCG.

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“…It is obvious that a misleading result may be obtained if different assays are used during monitoring of a patient with suspected ectopic pregnancy or threatening abortion during early pregnancy, when most of the hCG produced is hyperglycosylated. Specific detection of this form of hCG has been claimed to be of advantage for early detection of pregnancy and pregnancy-related disorders (12,13 ). It is reassuring to find that none of the assays failed to detect this form, and thus it is likely that problems will be encountered in pregnancy only when shifting assays during monitoring of the pregnancy.…”

mentioning

confidence: 99%

Standardization of Assays for Human Chorionic Gonadotropin

Stenman

2004

Clinical Chemistry

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Hyperglycosylated hCG (invasive trophoblast antigen, ITA) a key antigen for early pregnancy detection

Cited by 73 publications

References 25 publications

Quantitative, Wide-Range, 5-Minute Point-of-Care Immunoassay for Total Human Chorionic Gonadotropin in Whole Blood

Quantitative, Wide-Range, 5-Minute Point-of-Care Immunoassay for Total Human Chorionic Gonadotropin in Whole Blood

hCG and Hyperglycosylated hCG Carbohydrate Structure Corrected

Standardization of Assays for Human Chorionic Gonadotropin

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