Prevalence of Heterophilic Antibody Interference in Eight Automated Tumor Marker Immunoassays (Technical Briefs‪)‬

Heterophilic antibodies are human antibodies that can bind animal antibodies. They can cause problems in immunoassays, particularly immunometric assays, where they can form a bridge between the capture and detection antibodies, leading to a false-positive result in the absence of analyte or, if analyte is also present, to a false increase in measured concentrations. Very rarely, heterophilic antibodies can also lead to false-negative or falsely low results. By adding blocking reagents, assay manufacturers have reduced the incidence of heterophile interferences from the 2-5% observed in unblocked assays but have been unable to completely eliminate the problem (1, 2). During the last 10 years, tumor marker assays for human chorionic gonadotropin (hCG), prostate-specific antigen (PSA), cancer antigen 125 (CA 125), carcinoembryonic antigen, and calcitonin have all been reported to suffer from this problem, frequently with undesirable clinical outcomes (3-7).