False-Positive Cardiac Troponin T Due to Assay Interference with Heterophilic Antibodies

Shayanfar, N; Bestmann, L; Schulthess, G; Hersberger, M (2008). False-positive cardiac troponin T due to assay interference with heterophilic antibodies. Swiss Medical Weekly, 138(31-32):470. Postprint available at: http://www.zora.uzh.ch University of Zurich Posted at the Zurich Open Repository and Archive, University of Zurich. Zurich Open Repository and Archive http://www.zora.uzh.ch Originally published at: Swiss Medical Weekly 2008, 138(31-32):470.

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Year: 2008

False-positive cardiac troponin T due to assay interference with heterophilic antibodies

Shayanfar, N; Bestmann, L; Schulthess, G; Hersberger, M

Posted at the Zurich Open Repository and Archive, University of Zurich. http://www.zora.uzh.ch

Originally published at: Swiss Medical Weekly 2008, 138(31-32):470. 470 Shayan 12379.qxp 31.7.2008 5:49 Uhr Seite 470

Peer reviewed clinical letter SWISS MED WKLY 2008;138(31–32):470 · www.smw.ch 470470

False-positive cardiac Repeat measurements showed that serum testing for the presence of such heterophilic anti- concentration of troponin T remained elevated bodies in a patient’s sample. The suspected sam- troponin T due to assay (1.65 mg/l, 1.46 mg/l and 1.75 mg/l after two, six ple can be re-measured with an assay from an- and 48 hours, respectively) while levels of CK, other manufacturer and will usually give a dis- interference with CK-MB, and myoglobin remained within their cordant result, at least when assayed by a differ- reference ranges. ent two-site method [1]. Alternatively, the sample heterophilic antibodies In view of the persistently elevated serum can be re-analyzed after pre-treatment with concentrations of troponin T without elevation commercially available heterophilic blocking of other cardiac necrosis markers, we decided not reagents, as presented in this report [5, 6]. Noushin Shayanfara, Lukas Bestmanna,Georg to undertake coronary angiography suspecting Schulthessb, Martin Hersbergerc interference of heterophilic antibodies with the Correspondence: troponin T assay. To show such interference, we a Institute of Clinical Chemistry, University Martin Hersberger treated a serum sample of our patient with het- Hospital Zurich, Zurich, Switzerland Division of Clinical Chemistry erophilic blocking reagent (Scantibodies Labora- b Medical Policlinic, Department of Internal and Biochemistry tory, Santee, CA, USA) for one hour and meas- Medicine, University Hospital Zurich, Zurich, University Children’s Hospital Zürich ured troponin T again. The troponin T level de- Switzerland Steinwiesstrasse 75 creased to 0.18 mg/l upon treatment with the c Division of Clinical Chemistry and Biochem- CH-8032 Zürich blocking antibody while the same treatment did istry, University Children’s Hospital Zürich, Switzerland not alter the troponin T level in a sample from a Zurich, Switzerland E-Mail: [email protected] patient with acute coronary syndrome measured in parallel. These results confirmed antibody in- A 38-year-old woman was admitted to the emer- terference in the troponin assay. The patient was gency unit with chest pain radiating to her left discharged with the diagnosis of musculoskeletal arm. She had recently suffered from a cold with chest pain. cough and neck pain lasting for 2 weeks. The pa- The origin of the heterophilic antibodies is References tient had a history of deep venous thrombosis not clear. However, in a recent review Levinson during pregnancy associated with APC-resis- and Miller argued that they represent natural an- 1 Levinson SS, Miller JJ. Towards a better under- standing of heterophile (and the like) antibody tance. She had neither cardiovascular risk factors tibodies that bind their antigen with low affinity interference with modern immunoassays. [see nor a history of coronary or cerebral artery dis- [1]. This may explain why the older radioim- comment]. Clin Chim Acta. 2002;325(1-2): 1–15. ease. The family history was negative for coro- munoassay that depend on strong affinity bind- 2 Yeo KT, et al. Performance of the enhanced Ab- nary heart disease and stroke. ing of the antibodies were less prone to such in- bott AxSYM cardiac troponin I reagent in patients teractions than the newer generation immunoas- On admission the patient complained of with heterophilic antibodies. Clin Chim Acta. strong pain in the left side of the chest worsening says [1]. These modern immunoassays have been 2000;292(1-2):13–23. on inspiration. She had painful musculoskeletal revised by adding non-specific blocking antibod- 3 Klee GG. Human anti-mouse antibodies. points on the left chest wall and neck, otherwise ies to the assay to reduce the effect of interfering Archives of Pathology & Laboratory Medicine, physical examination was normal. Computed to- antibodies [2], however, some patients may ex- 2000;124(6):921–3. mography of the chest ruled out pulmonary em- ceed the blocking capacity of a specific im- 4 Kim WJ, et al. Performance of a revised cardiac bolism. Neither electrocardiogram nor echocar- munoassay procedure [3, 4]. troponin method that minimizes interferences diography showed any evidence of perimyocardi- It is estimated that heterophilic antibodies from heterophilic antibodies. Clin Chemistry. tis, myocardial ischaemia or cardiac infarction. cause about one false result in every 2000 investi- 2002;48(7):1028–34. However, elevated troponin T serum levels (1.76 gations produced with modern immunoassays 5 Preissner CM, et al. Prevalence of heterophilic mg/l) were detected (Elecsys E170, Roche Diag- [1]. This can result in unnecessary and possibly antibody interference in eight automated tumor nostic, Rotkreuz, Switzerland), while CK (90 even harmful diagnostic procedures and/or treat- marker immunoassays. Clin Chemistry. 2005;51 U/l, Modular P, Roche Diagnostic), CK-MB (13 ment. Therefore, physicians need to be aware of (1):208–10. U/l, Modular P, Roche Diagnostic), and myoglo- these interferences with immunoassays, which 6 Trojan A, et al. False-positive human serum chori- bin (29 U/l, Elecsys E170, Roche Diagnostic) basically can occur with every immunoassay. onic gonadotropin in a patient with a history of were within reference ranges. Contacting their laboratory directors will allow germ cell cancer. Oncology. 2004;66(4):336–8. Call for paper NEU.qxp:1. US SMW 38 28.2.2008 8:10 Uhr Seite 1

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