Charge variants in serum and urine hCG

Background: All serum and urine pregnancy tests sold in the United States are calibrated against the WHO 3rd and 4th International Standards (3rd and 4th I.S.) of Human Chorionic Gonadotropin (hCG). These standards have been isolated from pregnancy urine; however, they are used to calibrate, and generate antibodies used in both urine and serum hCG tests. hCG molecules may vary in sialic acid content; this changes the acidity of the molecule. Published studies have shown that these carbohydrate elements may alter recognition of hCG in different serum and urine hCG tests. We investigated the charge variants of hCG in serum and urine samples, and in hCG standards. Methods: Samples were analyzed by preparative isoelectric focusing. Charge variants of hCG were quantitated using the DPC Immulite hCG assay. Results: A difference was observed in the proportion of charge variants in urine and serum samples. There was a significantly higher proportion of more-acidic variants in the urine samples. Conclusions: Urine-derived standards may not be representative of serum hCG and therefore may not be appropriate for calibrating serum assays. Variation among hCG test results when using different immunoassays has been a persistent problem for years. Additional studies are needed to focus on the molecular dissimilarity of urine and serum hCG, as well as other factors, to determine their significance and contribution to the problem of interassay variation when comparing hCG results. (C) 2004 Elsevier B.V. All rights reserved.