Discordant results in human chorionic gonadotropin assays.

Discordance has been reported in human chorionic gonadotropin (hCG) concentrations measured by different immunoassay kits. We examined the results for 40 serum samples assayed with 10 different hCG immunoassay kits. Results varied considerably. Individual sample results varied by as much as 58-fold. Average results for different kits varied by as much as 1.4-fold for pregnancy (20 samples) and 2.2-fold for trophoblast disease (20 samples) serum. We investigated the causes of this discordance. hCG or hCG beta are general names for mixtures of hCG, hCG alpha, or hCG beta immunoreactive molecules in serum. These mixtures include regular hCG, nicked hCG (missing peptide linkages at beta 44-45 or beta 47-48), carbohydrate variants of hCG, hCG missing the beta-subunit C-terminal segment, free beta-subunit, beta-core fragment, and free alpha-subunit. We prepared standards for each of these major variants and measured their reactivities in the 10 hCG immunoassay kits. Free beta-subunit reactivity varied from nonrecognition (anti-beta:anti-alpha type kits; Hybritech Tandem-R and others) to overrecognition (one kit had five-fold greater affinity for free beta than for hCG). Kits with antibodies to beta-subunit C-terminal segment (Organon NML and others) failed to recognize hCG missing this segment, a component of serum hCG in trophoblast disease. Kits with anti-hCG antibodies (Serono MAIA-clone and others) had minimal recognition of nicked hCG (12%), a component of all serum hCG samples, and consistently gave the lowest values with all serum samples. We conclude that differences in recognition of nicked hCG, free beta, and these other hCG variants cause discordance in hCG immunoassay results.

[1]  L. Cole,et al.  Polypeptide nicks cause erroneous results in assays of human chorionic gonadotropin free beta-subunit. , 1992, Clinical chemistry.

[2]  L. Cole,et al.  The heterogeneity of human chorionic gonadotropin (hCG). I. Characterization of peptide heterogeneity in 13 individual preparations of hCG. , 1991, Endocrinology.

[3]  L. Cole,et al.  The heterogeneity of human chorionic gonadotropin (hCG). III. The occurrence and biological and immunological activities of nicked hCG. , 1991, Endocrinology.

[4]  L. Cole,et al.  The heterogeneity of human chorionic gonadotropin (hCG). II. Characteristics and origins of nicks in hCG reference standards. , 1991, Endocrinology.

[5]  J. Bidart,et al.  Occurrence of fragmentation of free and combined forms of the beta-subunit of human chorionic gonadotropin. , 1990, Endocrinology.

[6]  R. Sakakibara,et al.  A nicked beta-subunit of human chorionic gonadotropin purified from pregnancy urine. , 1990, Journal of biochemistry.

[7]  L. Cole,et al.  Serum HCG beta-core fragment is masked by associated macromolecules. , 1990, The Journal of clinical endocrinology and metabolism.

[8]  W. Hendrickson,et al.  Crystallization and characterization of human chorionic gonadotropin in chemically deglycosylated and enzymatically desialylated states. , 1989, Biochemistry.

[9]  L. Cole,et al.  The isomers, subunits and fragments of hCG , 1989 .

[10]  J. Bidart,et al.  Characterization of a cleavage product in the human choriogonadotropin β-subunit , 1988 .

[11]  T. Kitajima,et al.  Fragmentation of the beta-subunit of human chorionic gonadotropin produced by choriocarcinoma. , 1988, Endocrinology.

[12]  R. Canfield,et al.  Development of an assay for a biomarker of pregnancy and early fetal loss. , 1987, Environmental health perspectives.

[13]  R. Frydman,et al.  Physiological Studies of Human Chorionic Gonadotropin (hCG), αhCG, and βhCG as Measured by Specific Monoclonal Immunoradiometric Assays , 1987 .

[14]  L. Cole.  O-Glycosylation of Proteins in the Normal and Neoplastic Trophoblast , 1987 .

[15]  J. Wands,et al.  Sensitive and specific assay for human chorionic gonadotropin (hCG) based on anti-peptide and anti-hCG monoclonal antibodies: construction and clinical implications. , 1986, The Journal of clinical endocrinology and metabolism.

[16]  R. Hussa,et al.  Discordant Human Chorionic Gonadotropin Results: Causes and Solutions , 1985, Obstetrics and gynecology.

[17]  M. Segers,et al.  Discordant results for choriogonadotropin: a problem caused by lutropin beta-subunit interference? , 1985, Clinical chemistry.

[18]  E. Siris,et al.  Use of a highly sensitive and specific immunoradiometric assay for detection of human chorionic gonadotropin in urine of normal, nonpregnant, and pregnant individuals. , 1984, The Journal of clinical endocrinology and metabolism.

[19]  V. Caride,et al.  Discordant inter-kit results in the radioimmunoassay for choriogonadotropin in serum. , 1984, Clinical chemistry.

[20]  R. Hussa.  Procedure for discordant hCG results. , 1984, Clinical chemistry.

[21]  O. P. Bahl,et al.  Assignment of disulfide bonds in the beta subunit of human chorionic gonadotropin. , 1981, The Journal of biological chemistry.

[22]  矢崎 克己.  Isoelectric heterogeneity of human chorionic gonadotropin : presence of choriocarcinoma specific components , 1981 .

[23]  O. P. Bahl,et al.  Assignment of disulfide bonds in the alpha subunit of human chorionic gonadotropin. , 1980, The Journal of biological chemistry.

[24]  Hao‐Chia Chen,et al.  Limitations and Problems of hCG-Specific Antisera , 1980 .

[25]  G T Ross,et al.  A radioimmunoassay which specifically measures human chorionic gonadotropin in the presence of human luteinizing hormone. , 1972, American journal of obstetrics and gynecology.