Exploring the Role of Cardiac Troponin-Specific Autoantibodies: Prolonged Cardiac Troponin Elimination, Reduced Clearance, and Variable Interference across 5 Commercial Assays

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays are prone to negative and positive interferences caused by endogenous cardiac troponin-specific autoantibodies (cTnAAbs). Large macrotroponin complexes formed of cardiac troponin (cTn) and cTnAAbs may result in falsely elevated hs-cTn results. This is potentially due to reduced clearance of macrotroponin, but direct evidence is still lacking. In this study, we investigated the possible effects of cTnAAbs on the elimination of cTn. METHODS: Twenty patients with ST-elevation myocardial infarction (MI) underwent plasmapheresis within 24 h after revascularization to harvest plasma with a high cTn concentration. After clinical recovery, patients returned to the hospital for autologous plasma re-transfusion. Following re-transfusion, blood samples were collected at fixed time points and analyzed with 5 commercial hs-cTn assays. The presence of cTnAAbs in the samples and the epitope specificity of cTnAAbs were investigated with in-house immunoassays. RESULTS: Altogether, 2 out of 20 patients (10%) were cTnAAb-positive. With 4 commercial hs-cTn assays, cTnAAb-positive patients mainly showed longer elimination half-lives and slower cTn clearances than most cTnAAb-negative patients. One hs-cTn assay was prone to negative cTnAAb interference but correspondingly less prone to positive macrotroponin interference. The central part of cardiac troponin I (cTnI) was predominantly affected by cTnAAbs. CONCLUSIONS: Endogenous cTnAAbs were for the first time shown to prolong the elimination half-life and reduce the clearance of cTn in the circulation. Additionally, the extent of analytical interference from cTnAAbs and their reactivity to macrotroponin varies among commercial hs-cTn assays, an important consideration for laboratories to ensure accurate diagnosis of MI.