Comment on the Nature and Specificity of Bayer Corporation and Chiron Diagnostics hCG Immunoassays

¹ Dept. of Obstetrics & Gynecology, Yale University, 333 Cedar St., New Haven, CT 06520,
² Chiron Diagnostics, 333 Coney St., East Walpole, MA 02032, ,
³ Bayer Corporation, Diagnostics Division, 511 Benedict Ave., Tarrytown, NY 10591
^a Author for correspondence. E-mail laurence.cole{at}yale.com.

To the Editor:

We wish to update information in the recent hCG review article (1) , regarding the specificities and antibody configurations used in the Chiron Diagnostics and Bayer Corporation hCG immunoassays.

The review article depicted the diverse nature of the human chorionic gonadotropin (hCG) molecule. As described, a non-nicked hCG (the hormone), a nicked hCG, a free -subunit, and a free ß-subunit are present in blood samples, and the same molecules plus a ß-core fragment occur in urine samples.

As described in the review article (1) , commercial hCG assays sold in the United States use a variety of antibodies directed to different sites on hCG and related molecules. Some assays use antibodies to non-nicked hCG ("anti-hCG dimer"), others use antibodies to sites on hCG ß-subunit common to hCG and its free ß-subunit ("anti-common ß1" and "anti-common ß2"). Still other assays use antibodies to diverse epitopes on hCG subunits and fragments ("anti-common ", "anti ß C-terminal", "anti-free ß", and "anti ß-core fragment"). The combination of antibodies used by an hCG assay dictate the specificity of the assay and whether it detects non-nicked hCG only, non-nicked hCG and free ß-subunit, nicked and non-nicked hCG only, or nicked and non-nicked hCG with free ß-subunit and possibly ß-core fragment.

In Table 2 of the review article, examples were given of antibody configurations and of the likely specificities of 54 commercial hCG-related immunoassays sold in the United States (1) . The table was based totally on information in assay instruction booklets, on details from telephone technical support services, and on information published in reports. Here we make corrections to that table.

The Chiron Diagnostics Magic Lite^TM total hCG assay uses a combination of anti-common ß2 and anti-hCG dimer antibodies to capture antigens and an anti-common ß1 antibody to label the captured molecules. This combination of antibodies detects nicked and non-nicked hCG, free ß-subunit and urine ß-core fragment, or all hCGß-related molecules. The Chiron Diagnostics ACS:180^TM assay uses the same types of antibody, but with the capture and tracer antibodies reversed (anti-common ß1 capture antibody, with anti-common ß2 and anti-hCG dimer tracer antibodies). This assay also detects nicked and non-nicked hCG and free ß-subunit. It does not detect urine ß-core fragment.

The Bayer Corporation Immuno-1^TM hCG assay uses a similar mixture of antibodies. It uses a combination of an anti-common ß2 and anti-hCG dimer antibody to capture hCG and related molecules and an anti-common ß1 antibody to label captured molecules. This assay also detects nicked and non-nicked hCG and free ß-subunit. The table in the review article also listed a Bayer Immuno-1 ß-core fragment assay (1) . This assay is strictly a research assay and is not for sale.

As described in this and other review articles by Dr. Cole (1)(2)(3) , detection of nicked hCG, hCG missing the ß-subunit C-terminal, and free ß-subunit may be important for monitoring hCG immunoreactivity in patients with trophoblast disease, in patients with cancer, for pregnant women with aneuploid fetuses, and for following the clearance of hCG after parturition or termination of pregnancy. The Chiron Diagnostics Magic Lite and the Chiron Diagnostics ACS:180 total hCG assays and the Bayer Immuno-1 hCG assay detect these important hCG-related molecules and may be useful for these pregnancy- and cancer-related applications.

References

1. Cole LA. Immunoassay of hCG, its free subunits and metabolites. Clin Chem 1997;43:2233-2243. [Abstract/Free Full Text]
2. Cole LA. hCG, its free subunits and metabolites in pregnancy and trophoblastic disease. J Reprod Med 1998;43:3-10. [Web of Science][Medline] [Order article via Infotrieve]
3. Cole LA. Human chorionic gonadotropin (hCG), free (free ), free ß (free ß) and ß-core fragment (ß-core). Diagn Endocrinol Metab 1997;15:199-220.