Macrotroponin and antibody-mediated interference: An underrecognized cause of discordant cardiac troponin results

High-sensitivity cardiac troponin (hs-cTn) assays have improved the detection of myocardial injury, but have also increased the recognition of clinically discordant results. Among the causes of such discrepancies, analytical interferences remain underrecognized. Macrotroponin, a complex formed between cardiac troponin and immunoglobulins, represents a circulating immunoreactive complex of uncertain biological significance that remains analytically detectable and may lead to persistently elevated and non-dynamic cTn concentrations in the absence of myocardial injury.

This narrative review summarizes current clinical evidence on macrotroponin-associated interference in cTn immunoassays, predominantly derived from selected cohorts, case reports, and analytical studies. We describe proposed mechanisms, including autoantibody formation and immune complex persistence, and discuss assay-dependent variability. We examine key clinical scenarios in which macrotroponin should be suspected, including post-inflammatory states, autoimmune diseases, SARS-CoV-2-related settings, and physiological stress such as endurance exercise. Finally, we outline practical laboratory approaches for detection, including polyethylene glycol precipitation, immunoglobulin depletion, and size-exclusion techniques, and propose a clinically oriented diagnostic workflow.

Macrotroponin represents an important and often overlooked cause of persistent or discordant cTn elevation. Recognition of this phenomenon is essential to avoid misdiagnosis and unnecessary investigations. Integration of biomarker kinetics, clinical context, and targeted laboratory testing is critical for accurate interpretation. Further studies are needed to define its prevalence, biological determinants, and standardized diagnostic strategies.