Establishment, Value Assignment, and Characterization of New WHO Reference Reagents for Six Molecular Forms of Human Chorionic Gonadotropin

Bristow, Adrian; Berger, Peter; Bidart, Jean‐Michel; Birken, Steven; Norman, Robert J.; Stenman, Ulf‐Hǎkan; Sturgeon, Catharine M.

doi:10.1373/clinchem.2004.038679

Cited by 63 publications

(39 citation statements)

References 17 publications

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“…This recommendation is compatible with current thinking, in that the ideal metrological solution for heterogeneous analytes is to characterize and determine each of the components of the mixtures they comprise (4,9 ). In practice, although separate determination of the major forms has been shown to provide additional clinical information (7,10 ), most currently available hCG assays are designed to measure the main forms of hCG immunoreactivity together.…”

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confidence: 55%

“…In addition to the 4th IS (75/589), these included the IRR for hCG (99/ 688), nicked hCG (hCGn, IRR 99/642), hCG ␤-subunit (hCG␤, IRR 99/650), nicked hCG ␤-subunit (hCG␤n, IRR 99/692), and hCG ␤-core fragment (hCG␤cf, IRR 99/708). The IRRs were assigned values in substance concentrations (mol) (3,4 ).…”

Section: Methodsmentioning

confidence: 99%

“…The 6 isoforms were prepared by use of previously developed purification methods, which included hydrophobic interaction chromatography and reversed-phase HPLC (3 ). The high purity and homogeneity of the preparations-as confirmed by results of amino acid and sequence analyses, carbohydrate composition, electrophoretic patterns, and immunoassay studiessubsequently enabled their calibration in substance concentrations (i.e., molar units) (Table 1) (4,5 ).…”

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confidence: 99%

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Differences in Recognition of the 1st WHO International Reference Reagents for hCG-Related Isoforms by Diagnostic Immunoassays for Human Chorionic Gonadotropin

et al. 2009

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Background: The 1st WHO International Reference Reagents (IRRs) for 6 human chorionic gonadotropin (hCG)-related molecular variants, highly purified and calibrated in substance concentrations by the IFCC Working Group for hCG, permit experimental elucidation of what commercially available hCG methods measure in molar terms and enable assessment of their fitness for clinical purposes. Methods: Pools containing known amounts of the IRRs spiked into normal human serum were issued to participants through the UK National External Quality Assessment Service for hCG for a period of 7 years. Among 16 assays used, 4 recognized only hCG, whereas 6 recognized hCG and its free β-subunit (hCGβ), and 6 recognized hCG, hCGβ, and the beta core fragment. Results: Differences in calibration of current hCG assays are moderate. Mean recovery of the current International Standard (IS), hCG IS 75/589, was 107% (range 93% to 126%), whereas that of the IRR 99/688 for hCG was 139% (range 109%–164%). Between-method variation for the latter (CV 12.3%) was also greater than for IS 75/589 (CV 8.8%). Recognition of hCGβ varied markedly (CV 37%). Most assays overestimated it, but 2 RIAs produced results that were slight underestimations. Recognition of the beta core fragment was even more variable (CV 57%) and was closest to equimolarity for the RIAs. Conclusions: Assays for hCG show considerable variation in their recognition of various forms of hCG, and this variablility is the most important cause of method-related differences in hCG results in serum and an even more important cause of method-related differences in urine measurements. Equimolar recognition of the major hCG isoforms is essential if between-method comparability for hCG is to be improved.

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confidence: 55%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Differences in Recognition of the 1st WHO International Reference Reagents for hCG-Related Isoforms by Diagnostic Immunoassays for Human Chorionic Gonadotropin

et al. 2009

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“…The detection limit of the assay was 0.27 pmol/L, the upper reference limit for hCG␤ in serum was 2 pmol/L, and the CV was 2%-10% at concentrations above 3 pmol/L and Ͻ15% at concentrations of 1-3 pmol/L (13,18 ). The hCG␤ assay was calibrated against WHO International Reference Reagent (IRR) 99/650 (National Institute of Biological Standards and Control, South Mimms, UK) (22,23 ). In one sample with discordant results, hCG was also determined with the Siemens Immulite 2000 (Siemens Medical) and Roche Elecsys total hCG (Roche Diagnostics) assays, according to instructions.…”

Section: Serum Determinationsmentioning

confidence: 99%

Hyperglycosylated Human Chorionic Gonadotropin in Serum of Testicular Cancer Patients

et al. 2012

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BACKGROUND Hyperglycosylated human chorionic gonadotropin (hCG-h) contains larger and more complex carbohydrate chains than regular human chorionic gonadotropin (hCG). hCG-h is thought to be the major form of hCG produced by testicular cancers and it has been suggested to play a key role in tumor invasion, but studies on hCG-h in testicular cancer are limited. We studied whether serum hCG is hyperglycosylated, and whether measurement of hCG-h in serum offers clinical value in the management of testicular cancer. METHODS We determined the serum concentrations of hCG-h, hCG, and the free β subunit of hCG (hCGβ) by time-resolved immunofluorometric assays in 176 serum samples (preoperative n = 67, relapse n = 20, follow-up n = 89) obtained from 84 testicular cancer patients. We analyzed the association between preoperative serum concentrations of hCG, hCG-h, and hCGβ with known prognostic factors and progression-free survival time. RESULTS A major proportion of hCG was hyperglycosylated preoperatively, at relapse, and shortly after treatment. The serum concentrations of hCG-h and hCG correlated strongly with each other and had similar diagnostic value. The preoperative serum concentration of hCG-h correlated with prognostic factors and outcome in the same way as hCG. Increased preoperative hCGβ concentration predicted shorter progression-free survival. CONCLUSIONS Most of the hCG expressed by testicular cancers is hyperglycosylated and therefore it is important that hCG assays used for management of testicular cancer recognize hCG-h.

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“…The former includes a complex heterogeneous family of intact, dissociated or degraded hCG-related polypeptides differing in carbohydrate content (70,71). The cross-reactivity of these forms varies among different antibodies used in commercially available tests.…”

Section: Who International Unitsmentioning

confidence: 99%

Glycans as Biomarkers: Status and Perspectives

Janković¹

2011

Journal of Medical Biochemistry

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lanaca koji su kovalentno vezani za poli pep tidnu ki~mu. Dobro je poznat zna~aj prome na u glikozilaciji proteina za nastanak, razvoj i krajnji ishod razli~itih bolesti kod ljudi. Glikani se smatraju jedinstvenim strukturama za di jag nozu, i pra}enje toka bolesti. U »omics« eri, glikom, glika n ski analog proteoma i genoma, predstavlja mogu}i izvor no vih biomarkera. Kreiranje strategije za otkri}e biomarkera zahteva nove principe i platforme za analizu relativno malih koli~ina brojnih glikoproteina. O~ekuje se da glikomske teh no logije, koje su jo{ u razvoju, a koje obuhvataju razli~ite tipove masene spektrometrije i afinitivnih tehnika, rezultiraju novim analiti~kim procedurama u oblasti odre |i vanja bio markera. Najve}i izazovi za eksperimentalnu i kli ni~ku gliko pro teomiku su: pretraga razli~itih tipova gliko mo lekula, oda bir potencijalnih markera i njihova selekcija ili pre ~i{}a -vanje i identifikacija. Za ovo je neophodno razviti teh no logije koje }e omogu}iti visoku senzitivnost detekcije biomarkera kao i odgovaraju}u standardizaciju i validaciju novih metoda, kako bi se one mogle primeniti u laboratorijskom radu. Dalji razvoj na polju primenjene glikonauke zahteva integrisani sistemski pristup sa ciljem da se na pravi na~in iskoriste sve njene mo gu}nosti u dijagnostici.

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Establishment, Value Assignment, and Characterization of New WHO Reference Reagents for Six Molecular Forms of Human Chorionic Gonadotropin

Cited by 63 publications

References 17 publications

Differences in Recognition of the 1st WHO International Reference Reagents for hCG-Related Isoforms by Diagnostic Immunoassays for Human Chorionic Gonadotropin

Differences in Recognition of the 1st WHO International Reference Reagents for hCG-Related Isoforms by Diagnostic Immunoassays for Human Chorionic Gonadotropin

Hyperglycosylated Human Chorionic Gonadotropin in Serum of Testicular Cancer Patients

Glycans as Biomarkers: Status and Perspectives

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