Cardiac troponin-specific autoantibodies cause interference in cardiac troponin detection in two commercial high-sensitivity assays

Background Cardiac troponin-specific autoantibodies (cTnAAbs) are present in approximately 5-20% of the population including individuals with and without a history of cardiac events or diseases. Through formation of macrotroponin (the complex of cTnAAb and cardiac troponin), cTnAAbs can cause positive and negative interference in cardiac troponin (cTn) assays depending on the design of the assays. However, scientific data especially on the negative interference is very limited. Purpose This study investigated the effect of cTnAAbs on the performance of two commercial high-sensitivity cTn assays. Methods Lithium-heparin plasma from 23 cTnAAb-positive and 68 cTnAAb-negative apparently healthy individuals were included in this study. The presence of cTnAAbs in the samples was determined with an investigational immunoassay. High-sensitivity troponin T (hs-cTnT) was measured with Elecsys hs-cTnT assay (Gen 5, Roche Diagnostics) and high-sensitivity troponin I (hs-cTnI) with Atellica hs-cTnI assay (Siemens Healthineers). All samples were measured in original state and after spiking with 200 ng/L (not standardized for cTnT and cTnI assays) of native human cardiac troponin ITC complex. The median [25th-75th percentile] values were compared between cTnAAb-positive and cTnAAb-negative groups with Mann-Whitney U-test. Results In the original state, the samples of cTnAAb-positive individuals had significantly higher cTn levels than the samples of cTnAAb-negative individuals (cTnAAb-positive 6.4 ng/L [2.5-21.9 ng/L] vs. cTnAAb-negative 2.5 ng/L [2.5-4.5 ng/L], p<0.001) with the Atellica hs-cTnI assay. With Elecsys hs-cTnT assay the values were similar in both groups (cTnAAb-positive 4.7 ng/L [3.1-6.1 ng/L] vs. cTnAAb-negative 5.4 ng/L [3.8-8.1 ng/L], p=0.203) (Fig.1). For samples spiked with troponin ITC complex, the values were lower in cTnAAb-positive samples with both assays (Atellica hs-cTnI: cTnAAb-positive 309 ng/L [267-364 ng/L] vs. cTnAAb-negative 584 ng/L [544-605 ng/L] p<0.001; Elecsys hs-cTnT: cTnAAb-positive 76 ng/L [73-82 ng/L] vs. cTnAAb-negative 93 ng/L [86-100 ng/L], p<0.001. When compared to the median result of spiked cTnAAb-negative samples, Atellica hs-cTnI detected 53% [46-62%], and Elecsys hs-cTnT 82% [79-88%] of the added cTn in cTnAAb-positive samples (Fig.2). Conclusions This study shows for the first time that cTnAAbs can cause significant negative interference in cTn detection in Elecsys hs-cTnT and Atellica hs-cTnI assays. For Atellica hs-cTnI, cTnAAb-positive individuals can show falsely high results at baseline but also falsely low results with acute cTn release.