Key result
Fast skeletal troponin I is selectively elevated in muscular dystrophy and correlates with creatine kinase.
Why the study?
It was unclear whether muscle injury in Becker and Duchenne muscular dystrophy patients results in elevated circulating fast and/or slow skeletal troponin I isoforms.
Cross-Sectional (n=231)
Fast skeletal troponin I (TNNI2), but not slow skeletal troponin I (TNNI1), is elevated in the circulation of patients with Becker and Duchenne muscular dystrophy, correlating with creatine kinase levels.
TNNI2 may mark fast-fiber damage in DMD/BMD; leaves open its utility as a biomarker beyond CK pending longitudinal studies.
INTRODUCTION: One of the hallmarks of injured skeletal muscle is the appearance of elevated skeletal muscle proteins in circulation. Human skeletal muscle generally consists of a mosaic of slow (type I) and fast (type IIa, IIx/d) fibers, defined by their myosin isoform expression. Recently, measurement of circulating fiber-type specific isoforms of troponin I has been used as a biomarker to suggest that muscle injury in healthy volunteers (HV) results in the appearance of muscle proteins from fast but not slow fibers. We sought to understand if this is also the case in severe myopathy patients with Becker and Duchenne muscular dystrophy (BMD, DMD). METHODS: An enzyme-linked immunosorbent assay (ELISA) that selectively measures fast and slow skeletal troponin I (TNNI2 and TNNI1) was used to measure a cross-section of patient plasma samples from HV (N = 50), BMD (N = 49), and DMD (N = 132) patients. Creatine kinase (CK) activity was also measured from the same samples for comparison. RESULTS: TNNI2 was elevated in BMD and DMD and correlated with the injury biomarker, CK. In contrast, TNNI1 levels were indistinguishable from levels in HV. There was an inverse relationship between CK and TNNI2 levels and age, but no relationship for TNNI1. DISCUSSION: We define a surprising discrepancy between TNNI1 and TNNI2 in patient plasma that may have implications for the interpretation of elevated muscle protein levels in dystrophinopathies.
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Barthel et al. (2021) conducted a cross-sectional in Becker and Duchenne muscular dystrophy (n=231). Becker and Duchenne muscular dystrophy vs. Healthy volunteers was evaluated on Plasma levels of fast and slow skeletal troponin I (TNNI2 and TNNI1). Patients with Becker and Duchenne muscular dystrophy had elevated fast skeletal troponin I (TNNI2) levels correlating with creatine kinase, whereas slow skeletal troponin I (TNNI1) was not elevated.
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