Identification of macrotroponin T: findings from a case report and non-reproducible troponin T results
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Leo Lam
Abstract
Objectives
Macrotroponin is due to cardiac troponin (cTn) binding to endogenous cTn autoantibodies. While previous studies showed a high incidence of macrotroponin affecting cTnI assays, reports of macrotroponin T, particularly without cTnI reactivity, have been rare. Although the clinical significance of macrotroponin is not fully understood, macroenzymes and complexes are recognised to cause confusion in interpretation of laboratory results. The potential for adverse clinical consequences due to misinterpretation of affected results is very high.
Methods
We describe four cases of macrotroponin T with persistently low high sensitivity cTnT (hs-cTnT) by the 9 min compared to the 18 min variant of the assay. Three cases were serendipitously identified due to the use of a lot number of Roche hs-cTnT affected by non-reproducible results, necessitating measurement of cTnT in duplicate. We identified and characterised these macrotroponin specimens by immunoglobulin depletion (Protein A and PEG precipitation), mixing studies with EDTA and recombinant cTnT.
Results
In cases of macro-cTnT, a lower result occurred on the hs-cTnT using the 9 min compared to 18 min variant assay (ratio of 9–18 min hs-cTnT <0.80). Mixing studies with recombinant cTnT or EDTA demonstrated a difference in recovery vs. controls. One of these patients demonstrated a high molecular weight complex for cTnI and cTnT demonstrating a macrocomplex involving both cTn. This patient demonstrated a rise and fall in cTn when measured by several commercial assays consistent with genuine acute cardiac injury.
Conclusions
We identified several cases of macro-cTnT and described associated clinical and biochemical features.
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Research funding: There is no research funding recieved for this work.
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Author contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following three requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained for one of the case reports presented.
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Ethical approval: The research related to human use has complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ Institutional Review Board or equivalent committee (Counties Manukau Research Office, Approval Number: CM1242).
References
1. Thygesen, K, Alpert, JS, Jaffe, AS, Chaitman, BR, Bax, JJ, Morrow, DA, et al.. Fourth universal definition of myocardial infarction (2018). Circulation 2018;138:e618–51. https://doi.org/10.5603/KP.2018.0203.Suche in Google Scholar
2. Remaley, AT, Wilding, P. Macroenzymes: biochemical characterization, clinical significance, and laboratory detection. Clin Chem 1989;35:2261–70. https://doi.org/10.1093/clinchem/35.12.2261.Suche in Google Scholar
3. Lam, L, Ha, L, Chiu, W. Persistent increase in alkaline phosphatase. Clin Chem 2018;64:415–6. https://doi.org/10.1373/clinchem.2017.277251.Suche in Google Scholar
4. Wong, SL, Isserow, S, Pudek, M. Macrotroponin causing elevation in cardiac troponin I. Can J Cardiol 2014;30:956.e5–6. https://doi.org/10.1016/j.cjca.2014.03.037.Suche in Google Scholar
5. Chew-Harris, JS, Brennan, SO, Florkowski, CM, Troughton, R, George, PM. Deciphering a macro-troponin I complex; a case report. Clin Chem Lab Med 2017;55:e77–9. https://doi.org/10.1515/cclm-2016-0490.Suche in Google Scholar
6. Lam, L, Heron, C, Aspin, L, Ha, L, Kyle, CV. Change in troponin concentrations in patients with macrotroponin: an in vitro mixing study. Clin Biochem 2020;85:43–8. https://doi.org/10.1016/j.clinbiochem.2020.08.012.Suche in Google Scholar
7. Lam, L, Aspin, L, Heron, RC, Ha, L, Kyle, C. Discrepancy between cardiac troponin assays due to endogenous antibodies. Clin Chem 2020;66:445–54. https://doi.org/10.1093/clinchem/hvz032.Suche in Google Scholar
8. Karády, J, Mayrhofer, T, Ferencik, M, Nagurney, JT, Udelson, JE, Kammerlander, AA, et al.. Discordance of high-sensitivity troponin assays in patients with suspected acute coronary syndromes. J Am Coll Cardiol 2021;77:1487–99. https://doi.org/10.1016/j.jacc.2021.01.046.Suche in Google Scholar
9. Warner, JV, Lam, L. Macrotroponin probably contributes to a difference in patient stratification in suspected acute coronary syndromes. J Am Coll Cardiol 2021;78:295–6. https://doi.org/10.1016/j.jacc.2021.05.013.Suche in Google Scholar
10. Roche Diagnostics. Elecsys package insert Elecsys troponin T hs. Available from: https://pim-eservices.roche.com/eLD/web/pi/en/home [Accessed 16 Feb 2021].Suche in Google Scholar
11. Eriksson, S, Junikka, M, Laitinen, P, Majamaa-Voltti, K, Alfthan, H, Pettersson, K. Negative interference in cardiac troponin I immunoassays from a frequently occurring serum and plasma component. Clin Chem 2003;49:1095–104. https://doi.org/10.1373/49.7.1095.Suche in Google Scholar
12. Akhtar, Z, Dargan, J, Gaze, D, Firoozi, S, Collinson, P, Shanmugam, N. False-positive troponin elevation due to an immunoglobulin-G-cardiac troponin T complex: a case report. Eur Heart J - Case Rep 2020;4:1–5. https://doi.org/10.1093/ehjcr/ytaa082.Suche in Google Scholar
13. Tang, G, Wu, Y, Zhao, W, Shen, Q. Multiple immunoassay systems are negatively interfered by circulating cardiac troponin I autoantibodies. Clin Exp Med 2012;12:47–53. https://doi.org/10.1007/s10238-011-0141-x.Suche in Google Scholar
14. Vylegzhanina, AV, Kogan, AE, Katrukha, IA, Antipova, OV, Kara, AN, Bereznikova, AV, et al.. Anti-cardiac troponin autoantibodies are specific to the conformational epitopes formed by cardiac troponin I and troponin T in the ternary troponin complex. Clin Chem 2017;63:343–50. https://doi.org/10.1373/clinchem.2016.261602.Suche in Google Scholar
15. Park, JY, Jaffe, AS. Troponin autoantibodies: from assay interferent to mediator of cardiotoxicity. Clin Chem 2017;63:30–2. https://doi.org/10.1373/clinchem.2016.268920.Suche in Google Scholar
16. Eriksson, S, Halenius, H, Pulkki, K, Hellman, J, Pettersson, K. Negative interference in cardiac troponin I immunoassays by circulating troponin autoantibodies. Clin Chem 2005;51:839–47. https://doi.org/10.1373/clinchem.2004.040063.Suche in Google Scholar
17. Favresse, J, Bayart, J-L, Gruson, D, Bernardini, S, Clerico, A, Perrone, M. The underestimated issue of non-reproducible cardiac troponin I and T results: case series and systematic review of the literature. Clin Chem Lab Med 2021;59:1201–11. https://doi.org/10.1515/cclm-2020-1564.Suche in Google Scholar
18. Favresse, J, Cadrobbi, J, Eucher, C, Laffineur, K, Rosseels, C, Pieters, D. Non-reproducible cardiac troponin results occurring with a particular reagent lot. Clin Chem Lab Med 2020;59:e9-12. https://doi.org/10.1515/cclm-2020-0562.Suche in Google Scholar
19. Warner, JV, Marshall, GA. High incidence of macrotroponin I with a high-sensitivity troponin I assay. Clin Chem Lab Med 2016;54:1821–9. https://doi.org/10.1515/cclm-2015-1276.Suche in Google Scholar
20. Plebani, M, Mion, M, Altinier, S, Girotto, MA, Baldo, G, Zaninotto, M. False-positive troponin I attributed to a macrocomplex. Clin Chem 2002;48:677–9. https://doi.org/10.1093/clinchem/48.4.677.Suche in Google Scholar
21. Lam, L, Ha, L, Gladding, P, Tse, R, Kyle, C. Effect of macrotroponin on the utility of cardiac troponin I as a prognostic biomarker for long term total and cardiovascular disease mortality. Pathology 2021. https://doi.org/10.1016/j.pathol.2021.04.005. In press.Suche in Google Scholar
22. Pettersson, K, Eriksson, S, Wittfooth, S, Engstrom, E, Nieminen, M, Sinisalo, J. Autoantibodies to cardiac troponin associate with higher initial concentrations and longer release of troponin I in acute coronary syndrome patients. Clin Chem 2009;55:938–45. https://doi.org/10.1373/clinchem.2008.115469.Suche in Google Scholar
23. O’Donohoe, TJ, Ketheesan, N, Schrale, RG. Anti-troponin antibodies following myocardial infarction. J Cardiol 2017;69:38–45. https://doi.org/10.1016/j.jjcc.2016.07.018.Suche in Google Scholar
© 2021 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
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Artikel in diesem Heft
- Frontmatter
- Editorials
- Optimizing effectiveness of COVID-19 vaccination: will laboratory stewardship play a role?
- Mathematical recalibration of total bile acids: comparing the incomparable?
- Reviews
- Could metabolomics drive the fate of COVID-19 pandemic? A narrative review on lights and shadows
- Low free-T3 serum levels and prognosis of COVID-19: systematic review and meta-analysis
- Opinion Paper
- Pancreatic lipase: why laboratory community does not take enough care of this clinically important test?
- General Clinical Chemistry and Laboratory Medicine
- The BACH project protocol: an international multicentre total Bile Acid Comparison and Harmonisation project and sub-study of the TURRIFIC randomised trial
- Comparability of 11 different equations for estimating LDL cholesterol on different analysers
- Streamlined three step total vitamin C analysis by HILIC-UV for laboratory testing
- Hematology and Coagulation
- Anti-phosphatidyl-serine/prothrombin antibodies (aPS/PT) in isolated lupus anticoagulant (LA): is their presence linked to dual test positivity?
- Cancer Diagnostics
- Consideration should be given to smoking, endometriosis, renal function (eGFR) and age when interpreting CA125 and HE4 in ovarian tumor diagnostics
- Monitoring the M-protein of multiple myeloma patients treated with a combination of monoclonal antibodies: the laboratory solution to eliminate interference
- Cardiovascular Diseases
- Identification of macrotroponin T: findings from a case report and non-reproducible troponin T results
- Diabetes
- Impact of optimizing pre-analytical phase on the diagnosis of gestational diabetes and related outcomes
- Infectious Diseases
- Daily monitoring of viral load measured as SARS-CoV-2 antigen and RNA in blood, IL-6, CRP and complement C3d predicts outcome in patients hospitalized with COVID-19
- Alternative detection of SARS-CoV-2 RNA by a new assay based on mass spectrometry
- Performance evaluation of an automated SARS-CoV-2 Ag test for the diagnosis of COVID-19 infection on nasopharyngeal swabs
- Predicting the protective humoral response to a SARS-CoV-2 mRNA vaccine
- Quantitative serological evaluation as a valuable tool in the COVID-19 vaccination campaign
- Letters to the Editors
- Effects of various pre-analytical conditions on blood-based biomarkers of Alzheimer’s disease
- Stability of lactate in venous blood gas and sodium fluoride-potassium oxalate plasma: a 6-year retrospective database analysis
- Validation of the Fujirebio Lumipulse G1200 aldosterone assay for measurements during adrenal venous sampling for primary hyperaldosteronism
- The new Roche Elecsys TSH assay conforms with current IFCC C-STFT standards
- Development of an inverse-PCR approach for characterization of the major BCR-ABL1 breakpoint sequences on genomic DNA: proof of concept
- Antiphospholipid antibodies quantification using ALBIA technology: how to define an optimal cutoff?
- Simultaneous occurrence of EDTA-dependent lymphoagglutination and agglutination of myeloid cells in a patient with chronic myelomonocytic leukemia
- NT-proBNP use in old patients and the impact of the selected threshold value: a big data analysis
- Congress Abstracts
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