Selection of Antibodies and Epitopes for Cardiac Troponin Immunoassays: Should We Revise Our Evidence-Based Beliefs?(Editorials‪)‬

Cardiac troponins are regarded as the most specific and sensitive of the currently available diagnostic techniques for detection of myocardial damage, and the redefined criteria used to classify acute coronary syndrome patients presenting with ischemic symptoms as myocardial infarction patients are heavily predicated on an increased concentration of these markers in blood (1). Troponins also are the only markers identifying high-risk coronary patients who should be treated with antithrombotic agents, such as glycoprotein IIb/IIIa antagonists, and referred for invasive evaluation at the earliest opportunity. Not all troponin assays, however, are created equal; therefore, method selection by the clinical laboratory represents one of the major factors influencing the performance of this important biomarker for the diagnostic classification of an individual patient. Recent experimental data indicated that various commercially available methods have different limits of detection (and imprecision) for cardiac troponins (2). Thus, the percentage of patients recategorized from angina to myocardial infarction based on troponin results as a diagnostic criterion is also critically dependent on the performance of the assay used (3). Formulation of assay reagents is also important in minimizing analytic interference. Falsely increased or decreased troponin results may occur because of interferences with the antigen-antibody reaction. Interferences from rheumatoid factors or human anti-mouse antibodies, which can mimic troponin by linking the capture and detector antibodies, have been reported (4). Icteric and hemolyzed serum samples might also be a problem in certain immunoassays (5). Finally, an interfering blood component inhibiting the binding of some antibodies against epitopes in the central part of the cardiac troponin I (cTnI) molecule has been described (6,7). The use of antibodies recognizing these epitopes, which are known to be less susceptible to proteolysis, has been recommended for the development of cTnI assays (8), and many manufacturers have now endorsed this recommendation. Thus, the authors of studies on the negatively interfering factor predicted that many cTnI assays were likely to be affected by the factor. More and definitive experimental evidence was, however, required to permit identification and isolation of this component (9).