Troponin-Specific Autoantibody Interference in Different Cardiac Troponin I Assay Configurations

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 2012-06, Vol.58 (6), p.1040-1048
• Main Authors: SAVUKOSKI, Tanja, ENGSTRÖM, Emilia, ENGBLOM, Janne, RISTINIEMI, Noora, WITTFOOTH, Saara, LINDAHL, Bertil, EGGERS, Kai M, VENGE, Per, PETTERSSON, Kim
• Format: Article
• Language: English
• Subjects: Acute Coronary Syndrome - blood; Acute coronary syndromes; Analytical, structural and metabolic biochemistry; Autoantibodies - blood; Biological and medical sciences; Cardiology; Cloning; Colleges & universities; Epitopes; False Negative Reactions; False Positive Reactions; Fundamental and applied biological sciences. Psychology; Humans; Immunoassay; Immunoassays; Investigative techniques, diagnostic techniques (general aspects); Life sciences; Medical sciences; Molecular biophysics; Multicenter Studies as Topic; Prospective Studies; Proteins; Radiometers; Sensitivity and Specificity; Troponin I - blood; Troponin I - immunology
• ISSN: 0009-9147; 1530-8561; 1530-8561
• DOI: 10.1373/clinchem.2011.179226

Autoantibodies to cardiac troponins (cTnAAb) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays. The aim of this study was to explore the degree of cTnAAb interference in different cTnI assay configurations. Ternary troponin complex was added into samples (serum or plasma, n = 132, 68% cTnAAb positive) from individuals without known cardiac conditions. The recovery of cTnI was then measured with 6 investigational cTnI assays (2, 3, or 4 antibodies per assay). Three of these assays were then selected for further comparison by use of samples (plasma, n = 210, 33% cTnAAb positive) from non-ST-elevation acute coronary syndrome patients in the FRISC-II (FRagmin/Fast Revascularisation during InStability in Coronary artery disease) cohort. Finally, these results were compared to those obtained with 3 commercial cTnI assays. Analytical recoveries varied widely among the 6 investigational assays. Notably the low recoveries (median 9%) of the midfragment-targeting reference assay were normalized (median 103%) with the use of the 4-antibody assay construct (3 capture, 1 tracer antibody) with only 1 antibody against a midfragment epitope. Reduced analytical recoveries correlated closely with measured autoantibody amounts. cTnI concentrations from cTnAAb-positive patient samples determined with 3 investigational assays confirmed the reduced concentrations expected from the low analytical recoveries. The results from the commercial cTnI assays with antibody selections representative for contemporary assay constructs revealed a similar underestimation (up to 20-fold) of cTnI in cTnAAb-positive samples. A novel cTnI assay deviating from the conventional IFCC-recommended midfragment approach substantially improves cTnI detection in samples containing cTnAAbs.