Standardization of Epitopes for human chorionic gonadotropin (hCG) Immunoassays

Berger, P. and Lapthorn, A. (2016) Standardization of Epitopes for human chorionic gonadotropin (hCG) Immunoassays. Current Medicinal Chemistry, 23(30), pp. 3481-3494. (doi:10.2174/0929867323666160530145503) (PMID:27237818)

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Abstract

hCG and its variants are markers for pregnancy tests, pregnancy-related complications, trophoblastic diseases, pre-natal screening of Down’s syndrome and doping controls. Strong demands are imposed on diagnostic methods by the dynamic changes in the absolute and relative levels of hCG protein backbone variants and glycosylation isoforms in serum and urine during development of pregnancy or the progression/remission of tumors. Observed differences in the results between commercial diagnostic immunoassays reflect the unequal molar recognition of the different metabolic hCG variants, in particular the hCG beta core fragment (hCGβcf), by the diagnostic antibodies (Abs), as their epitopes are not standardized, and the fact that suboptimal hCG standards are used. To rapidly characterize Abs by their epitope recognition and specificity to evaluate their suitability for diagnostic immunoassays a procedure of comparative epitope mapping has been developed using epitope-defined reference Abs. Comparative epitope mapping of diagnostic Abs will provide the basis for the harmonization standardization of diagnostic antigenic domains/epitopes and consequently for improved reliability of hCG measurements. Diagnostic first line assays will likely consist of pairs of Abs that recognize specific epitopes at the top of the neighboring peptide loops 1 and 3 (Ł1+3) and the cystine knot (ck) of hCGβ, respectively. In future significant improvements of reliability, robustness and comparability of the results of immunoassays for complex glycoproteins such as hCG will be achieved by the use (i) of standardized diagnostic Abs against well-defined epitopes and (ii) of the new International Standards for hCG and for five hCG variants established by WHO, that are calibrated in molar (SI) units.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lapthorn, Dr Adrian
Authors: Berger, P., and Lapthorn, A.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Current Medicinal Chemistry
Publisher:Bentham Science Publishers Ltd.
ISSN:0929-8673
ISSN (Online):1875-533X
Published Online:01 January 2016

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