Falsely elevated serum follicle-stimulating hormone levels in the context of heterophilic interference and response of these patients to IVF/ICSI: case reports
Keywords:Heterophilic antibody, FSH, LH, Heterophile Blocking Reagent (HBR)
AbstractHeterophilic antibodies can introduce errors in commonly used immunoassays, including those used for the peptide hormones FSH and LH. Heterophilic antibodies are human antibodies that can bind animal antibodies. They can cause problems in immune assays, particularly immunometric assays where they can form a bridge between capture and detection antibodies leading to false increase in measured concentrations. Serum FSH levels, as detected by immunoassay kits, have been recognized as a useful diagnostic and prognostic tool in reproductive medicine because they are a reliable marker of the ovarian follicular status and a predictor of the ovarian response to controlled ovarian hyperstimulation. Hence, the possibility of falsely elevated FSH levels due to heterophilic interference must be taken into account. Here, we report six cases positive for heterophilic antibodies whose serum samples had initial FSH values more than 10 IU/ml. They were subjected to repeat analysis as their antral follicle count and AMH were within normal limits. The repeat values were high and then serum samples were studied in dilution. Blood samples for FSH were also sent for interlab check. The samples showed significant lowering of values in both dilution and interlab checks and then subjected to the heterophilic antibody detection test. The detection of heterophilic antibodies appears to be Kit specific as interlab check give significantly different values. Out of the six patients, three patients underwent IVF/ICSI treatment with two of the three showing normal response. Interference with heterophilic antibodies must be thought of in case of discrepancy between the clinical context and biological markers obtained with immunoassays.
Bolstad N, Warren DJ, Nustad K. Heterophilic antibody interference in immunometric assay. Best Pract Res Clin Endocrinol Metab Oct. 2013;27(5):647-61.
Levinson SS, Miller JJ. Towards a better understanding of heterophile (and the like) antibody interference with modern immunoassays. Clin Chim Acta. 2002;325(1-2):1-15.
Warren DJ, Bjerner J, Paus E, Bormer OP, Nustad K. Use of an in vivo biotinylated single chain antibody as capture reagent in an immunometric assay to decrease the incidence of interference from heterophilic antibodies. Clin Chem. 2005;51(5):830-8.
Bjerner J, Olsen KH, Bormer OP, Nustad K. Human heterophilic antibodies display specificity for murine IgG subclasses. Clin Biochem. 2005;38(5):465-72.
Webster R, Fahie-Wilson M, Barker P, Chatterjee VK, Halsall DJ. Immunoglobulin interference in serum follicle-stimulating hormone assays: autoimmune and heterophilic antibody interference. Ann Clin Biochem. 2010;47(Pt4):386-9.