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1 Department of Biotechnology, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland.
2 Laboratory and
3 Department of Internal Medicine, Oulu University Hospital, PL 500, FIN-90029 OYS, Finland.
4 Department of Clinical Chemistry, Helsinki University Central Hospital, Haartmaninkatu 2, FIN-00290 Helsinki, Finland.
aAuthor for correspondence. Fax 358-2-333-8050; e-mail susann.eriksson{at}utu.fi.
Background: Cardiac troponin I (cTnI) is a sensitive marker of cardiac injury, but cTnI assays, like other immunoassays, are susceptible to interferences. We evaluated the presence of interfering substances by measuring the recovery of cTnI added to samples from volunteers and from patients with acute coronary syndromes (ACS).
Methods: We added a ternary complex of human cardiac troponin (30500 µg/L) or cTnI from serum to samples from healthy volunteers and ACS patients. We measured cTnI with a two-site sandwich time-resolved immunofluorometric assay using two antibodies against epitopes in the central stable part of cTnI. We also analyzed 108 heparin-plasma samples from 16 ACS patients with this assay, with an assay based on four antibodies, and with two commercial cTnI assays, AxSYM and ACS:180.
Results: In samples from both healthy persons and ACS patients, recoveries for our assay were 1167% (range). Recoveries were increased by addition of an antibody with an epitope in the N-terminal region of cTnI to the solid phase and an antibody with an epitope in the C-terminal region as a second detection antibody. In 2 of 16 patients with ACS, normal cTnI concentrations found when measured with the original assay demonstrated clinically abnormal (up to 10-fold higher) results with the additional N- and C-terminal antibodies in the early phase of infarction. Both commercial cTnI assays also demonstrated clinically misleading, falsely low cTnI concentrations.
Conclusions: Some yet unidentified, variable component, present in the blood from healthy volunteers and ACS patients, interferes with the binding of antibodies against epitopes in the central part of cTnI used in two commercial assays. Our approach to supplement the mid-fragment cTnI antibodies with antibodies in the N- and C-terminal parts of the molecule in an experimental assay represents a step in resolving this interferent.
The following articles in journals at HighWire Press have cited this article:
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Q. Lam, M. Black, O. Youdell, H. Spilsbury, and H.-G. Schneider Performance Evaluation and Subsequent Clinical Experience with the Abbott Automated Architect STAT Troponin-I Assay Clin. Chem., February 1, 2006; 52(2): 298 - 300. [Abstract] [Full Text] [PDF] |
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S. Eriksson and K. Pettersson Beliefs in Cardiac Troponin Testing Clin. Chem., September 1, 2005; 51(9): 1755 - 1756. [Full Text] [PDF] |
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M. Panteghini Selection of Antibodies and Epitopes for Cardiac Troponin Immunoassays: Should We Revise Our Evidence-Based Beliefs? Clin. Chem., May 1, 2005; 51(5): 803 - 804. [Full Text] [PDF] |
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S. Eriksson, T. Ilva, C. Becker, J. Lund, P. Porela, K. Pulkki, L.-M. Voipio-Pulkki, and K. Pettersson Comparison of Cardiac Troponin I Immunoassays Variably Affected by Circulating Autoantibodies Clin. Chem., May 1, 2005; 51(5): 848 - 855. [Abstract] [Full Text] [PDF] |
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S. Eriksson, H. Halenius, K. Pulkki, J. Hellman, and K. Pettersson Negative Interference in Cardiac Troponin I Immunoassays by Circulating Troponin Autoantibodies Clin. Chem., May 1, 2005; 51(5): 839 - 847. [Abstract] [Full Text] [PDF] |
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S. Eriksson, J. Hellman, and K. Pettersson Autoantibodies against Cardiac Troponins N. Engl. J. Med., January 6, 2005; 352(1): 98 - 100. [Full Text] [PDF] |
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F Jishi, P R Hudson, C P Williams, R P Jones, G K Davies, Z R Yousef, R J Trent, and R P W Cowell Troponin I, laboratory issues, and clinical outcomes in a district general hospital: crossover study with "traditional" markers of myocardial infarction in a total of 1990 patients J. Clin. Pathol., October 1, 2004; 57(10): 1027 - 1032. [Abstract] [Full Text] [PDF] |
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F. Pagani, F. Stefini, and M. Panteghini Innotrac Aio! Second-Generation Cardiac Troponin I Assay: Imprecision Profile and Other Key Characteristics for Clinical Use Clin. Chem., July 1, 2004; 50(7): 1271 - 1272. [Full Text] [PDF] |
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S. Eriksson and K. Pettersson The Interfering Component in Cardiac Troponin I Immunoassays Clin. Chem., June 1, 2004; 50(6): 1101 - 1102. [Full Text] [PDF] |
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M. Panteghini The Interfering Component in Cardiac Troponin I Immunoassays: Need for Further Experimental Evidence Clin. Chem., March 1, 2004; 50(3): 676 - 677. [Full Text] [PDF] |
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