Diseased skeletal muscle: A noncardiac source of increased circulating concentrations of cardiac troponin T

Allan S. Jaffe, Vlad C. Vasile, Margherita Milone, Amy K. Saenger, Kalen N. Olson, Fred S. Apple

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

Abstract

Objectives: The purpose of this study was to determine whether there is immunoreactive cardiac troponin T (cTnT) expression in diseased skeletal muscle that might cause possible false-positive increases in cTnT. Background: Cardiac troponin (I or T) is the biomarker of choice for the diagnosis of cardiac injury. Recently, we were presented with a case that challenged the specificity of cTnT. Methods: Patients with myopathies seen in the Neuromuscular Clinic at the Mayo Clinic were screened for increases in cTnT. If present, an assay for cTnI was performed. If normal, skeletal biopsy tissue was obtained for Western blot analysis using the capture and detection antibodies from both the fourth-generation and high-sensitivity cTnT assays. Results were compared with findings in normal cardiac tissue. Results: Sixteen patients had increases in cTnT but not cTnI. All had a myopathy by clinical evaluation, clinical testing, and biopsy. Four residual biopsy samples were obtained. All 3 antibodies used in the cTnT (M11.7, M7) and high-sensitivity cTnT (5D8, M7) assays were immunoreactive with a 37- to 39-kDa protein in all 4 diseased skeletal muscle biopsy specimens and in cardiac tissue. A second immunoreactive isoform (34 to 36 kDa) was also found in 1 patient. None of the noncardiac control tissues expressed immunoreactive protein. Conclusions: These results document that there are forms in diseased skeletal muscle that could cause increases in circulating levels of cTnT. These increases could reflect re-expressed isoforms. Clinicians need to be aware of the possibility that noncardiac increases in cTnT may occur and lead to a possible false-positive diagnosis of cardiac injury when skeletal muscle pathology is present.

Original languageEnglish (US)
Pages (from-to)1819-1824
Number of pages6
JournalJournal of the American College of Cardiology
Volume58
Issue number17
DOIs
StatePublished - Oct 18 2011

Bibliographical note

Funding Information:
Funding for the Western blot experiments was supported by an AACC Van Slyke Foundation Research Grant to KNO. Dr. Jaffe is a consultant for Beckman, Radiometer, Critical Dx, Amgen, Siemens, and Alere; and has received speaker's fees from Roche and Abbott. Dr. Apple serves as a principal investigator for industry-sponsored research studies for the following companies that manufacture cTnI and cTnT assays: Roche Diagnostics, Alere, Siemens, BD, Radiometer, Abbott Diagnostics, Instrumentation Laboratories, Beckman Coulter, and BRAHMS; and is a paid consultant to 3 diagnostic companies that market cTnI assays: Instrumentation Laboratories, Abbott Diagnostics, and Ortho-Clinical Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.

Keywords

  • immunoblotting
  • skeletal muscle
  • troponin T

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