Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency

Knight, Adina Kay; Bingemann, Theresa; Cole, Laurence A.; Cunningham‐Rundles, Charlotte

doi:10.1111/j.1365-2249.2005.02837.x

Cited by 28 publications

(12 citation statements)

References 50 publications

(47 reference statements)

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“…Finally, clinical biochemistry laboratories should be aware that IgA de¢ciency has been reported to interfere with the determination of beta human chorionic gonadotrophin (bHCG) in some assays. 88 …”

Section: Resultsmentioning

confidence: 99%

The clinical significance of immunoglobulin A deficiency

2007

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Section: Resultsmentioning

confidence: 99%

The clinical significance of immunoglobulin A deficiency

2007

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“…These are called heterophilic antibodies. Humans with recent exposure to mononucleosis can be prone to develop HAAAs and those with IgA deficiency syndrome often have false positive assay problems due to heterophilic antibodies [ 186 ]. Each human antibody is bivalent so if an HAAA or heterophilic antibody is present in a person's serum it can bind and link together the immobilized and tracer antibodies making a capture antibody-heterophilic antibody-tracer antibody complex or a capture antibody-HAAA-tracer antibody complex.…”

Section: Hcg Immunoassaysmentioning

confidence: 99%

New discoveries on the biology and detection of human chorionic gonadotropin

Cole

2009

Reprod Biol Endocrinol

242

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Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG.For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis.While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy.New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic disease, diagnosing placental site trophoblastic tumor, managing testicular germ cell malignancies, and monitoring other human malignancies. There are very few molecules with such wide and varying functions as regular hCG and its variants, and very few tests with such a wide spectrum of clinical applications as total hCG.

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“…Sera of patients with IgA deficiency often contain heterophilic antibodies, possibly related to increased mucosal antigen exposure of the systemic circulation. Up to 30% of IgA-deficient sera led to false-positive hCG results as measured in three different assays [29]. Despite the incorporation of nonspecific blocking antibodies (Scantibodies Laboratory, Inc.) in the DPC hCG assay, 7.4% of the sera of IgA-deficient women showed false-positive results, again illustrating the imperfect nature of this modified assay.…”

Section: Review Of the Literaturementioning

confidence: 99%

False-Positive Serum Human Chorionic Gonadotropin (hCG) in a Male Patient with a Malignant Germ Cell Tumor of the Testis: A Case Report and Review of the Literature

et al. 2008

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A 39-year-old male patient with a favorable prognosis stage IIB metastatic malignant germ cell tumor (GCT) and elevated pre-and postorchiectomy serum human chorionic gonadotropin (hCG) was treated with three courses of combination chemotherapy resulting in a rapid normalization of his serum hCG.Within 2 months after the cessation of chemotherapy, his serum hCG increased again, suggesting tumor recurrence. Pathological examination of the resected residual retroperitoneal lymph nodes revealed no vital tumor cells. Based on the further rise in his serum hCG and enlargement of mediastinal lymph nodes on computed tomography scan, the patient underwent second-and third-line chemotherapy, which did not result in normalization of his serum hCG. Reanalysis of stored serum samples with other immunoassays revealed that the elevated serum hCG levels collected before first-line chemotherapy were indeed elevated, but those collected after first-line chemotherapy were all falsely positive. Currently, the patient is still alive and disease free. This is the first report of a male cancer patient who received unneeded second-and third-line chemotherapy for relapse based on false-positive hCG results. We discuss the pitfalls of false-positive serum hCG measurements, including heterophilic antibodies, as in our IgA-deficient patient, and review the literature. The Oncologist 2008;13:1149 -1154

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Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency

Abstract: SummaryA patient with IgA deficiency had a series of positive serum pregnancy tests which led to medical and surgical procedures for suspected molar pregnancy. These tests were found to be falsely positive due to heterophile antibody. The

Cited by 28 publications

References 50 publications

The clinical significance of immunoglobulin A deficiency

The clinical significance of immunoglobulin A deficiency

New discoveries on the biology and detection of human chorionic gonadotropin

False-Positive Serum Human Chorionic Gonadotropin (hCG) in a Male Patient with a Malignant Germ Cell Tumor of the Testis: A Case Report and Review of the Literature

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