False Increase of Cardiac Troponin I with Heterophilic Antibodies

The effects on immunoassays of heterophilic antibodies (HAs) in the plasma and serum have been well documented (1)(2)(3)(4)(5). The use of monoclonal mouse antibodies for radioimaging of tumors as well as in the treatment of some cancers often gives rise to human anti-mouse antibodies. HAs can also arise as a result of incidental or occupational exposure to foreign proteins, as in the case of veterinarians, farm workers, and food preparers, or by the presence of domestic animals in the home environment. The prevalence of HAs in the general population has been estimated to be as high as 40% (1). Typically, these antibodies are of the IgG class and recognize epitopes on the Fc portion of the foreign immunoglobulin, although instances where the epitope is located in the Fab region have been reported (6)(7). Additionally, the binding of these antibodies is not always species-specific, making it possible that antigens from two different species can be cross-linked. Although usually not clinically significant, the presence of high titers of these antibodies can lead to analytical errors in commonly used “sandwich” immunoassays by cross-linking the capture and label antibodies in the absence of specific analyte. Such cross-linking by HAs has been shown to lead to falsely increased CK-MB and CA125 (6)(7)(8). Most modern immunoassays contain nonspecific, “blocker” immunoglobulins originating from the same species as the analyte-specific antibodies in an attempt to limit the effect of HAs; however, the problem persists. We report here a 69-year-old man whose plasma and serum cardiac troponin I (cTnI) concentrations were falsely increased when measured using the Abbott AxSYM® cTnI assay. We demonstrate that HAs accounted for the falsely increased cTnI, and we suggest how to resolve such situations. A 69-year-old Caucasian man …