Cardiac troponin and β-type myosin heavy chain concentrations in patients with polymyositis or dermatomyositis
Introduction
The polymyositis (PM) and dermatomyositis (DM) complex encompasses a heterogeneous group of acquired muscle diseases called inflammatory myopathies. Muscle weakness and inflammatory infiltrates within the skeletal muscles are the principal clinical and histological findings. The incidence of PM, DM, and inclusion-body myositis is approximately 1 in 100,000 [1]. Clinical evidence of cardiac involvement in PM/DM patients has been reported in approximately 50% of cases [2]. Because of the ongoing destruction and regenerating processes in these chronic muscular diseases, serum enzyme activities of so-called cardiac enzymes, such as creatine kinase isoenzyme MB (CKMB) and lactate dehydrogenase 1 (LDH-1), are increased due to release from skeletal muscle [3], [4]. Creatine kinase (CK) consists of three isoenzymes, designated MM, MB, and BB. Skeletal muscle contains essentially CK-MM, but CK-MB can be also present [5]. During chronic regeneration of skeletal muscle the expression of the CK-B subunit is upregulated, which leads to an increased release of both, CK-BB and CK-MB, from skeletal muscle into the bloodstream [6]. In these disorders, abnormal serum CKMB cannot be used for diagnosing myocardial damage [7]. Determinations of the cardiac isoforms of troponin T (cTnT) and troponin I (cTnI) in serum are claimed to have the highest specificities of the available markers of myocardial damage [8], [9], [10], [11]. Because recent reports on cTnT increase in patients with PM or DM without evidence of ischaemic myocardial damage and increased cTnT concentrations in the absence of elevated cTnI concentrations in patients with chronic myopathies, questions have been raised as to the specificity of cTnT for cardiac damage in these disorders [12], [13]. Troponin T and troponin I both exist in three different isoforms with an unique structure, one for slow-twitch skeletal muscle, one for fast-twitch skeletal muscle and one for cardiac muscle [14], [15]. The three isoforms are encoded by three different genes. cTnI has an extra 31 amino acid residues at the N-terminus and its amino acid sequence shows about 40% dissimilarity from both other isoforms [15]. cTnT differs only by 6–11 amino acid residues from its skeletal muscle isoforms. Only 10–30% of the amino acid sequence show low homology [14]. Therefore, it is more difficult to produce cardiac-specific anti cTnT antibodies. However, both cTnI assays and the second generation cTnT assay show no cross-reactivity with skeletal troponins [8], [9], [10].
cTnI is never expressed in skeletal muscle, neither during fetal development nor in adult skeletal muscle in response to any pathological stimuli [16], [17]. cTnT is expressed in small amounts in skeletal muscle during fetal development. Most importantly, cTnT is not found in adult skeletal muscle [18]. cTnT has been found by immunofluorescence staining in regenerating or denervated rat skeletal muscle, probably due to reversion to a fetal-like pattern of expression of TnT isoforms [19]. Whether adult human skeletal muscle in response to any pathological stimuli re-expresses the cTnT isoform, and whether such a response is of clinical relevance remain to be further elucidated [20].
Myoglobin is an oxygen binding protein of striated muscles that is rapidly released after muscle damage. Myoglobin facilitates oxygen diffusion in striated muscle fibres. It is found most abundantly in striated muscles (heart and skeletal muscle), where it accounts for 5% to 10% of all cytoplasmatic proteins. It is located close to the sarcolemma, to the contractile apparatus, and to intracellular membranous or fibrillar structures. In skeletal muscle, myoglobin is found mainly in the slow-twitch “red” fibres. It is an established early marker of acute muscle damage [21].
Myosin is a hexameric structurally bound contractile protein containing four light and two heavy chains. MHC can be cleaved into its subfragments by enzymes. The rod portion can be further degraded to form light meromyosin and subfragment 2 [22]. An increase in plasma MHC concentration is an indicator of membrane leakage and degradation of the contractile apparatus [23]. Cardiac β-type MHC is coexpressed in slow-twitch skeletal muscle fibres.
The present study was carried out to evaluate new and established markers of cardiac and skeletal muscle damage in patients with PM or DM, i.e. cardiac troponins, myosin heavy chains, myoglobin, CK, and CKMB.
Section snippets
Subjects
Blood samples from 39 patients (35 females, 4 males, age 40±23 years, disease duration 20±22 months) were studied. All patients fulfilled the criteria of Bohan and Peter [24] for PM or DM. There were 22 patients with primary PM, 15 patients with primary DM and 2 patients with myositis and systemic sclerosis in overlap. Diagnosis of myositis was confirmed by muscle biopsy, electromyography, and laboratory investigations (LDH, C-reactive protein). The global clinical assessment was based on a
Results
No patient had clinical evidence for acute cardiac damage as assessed by ECG and echocardiogram as well as clinical presentation. Table 1 shows the results of laboratory markers and muscle injury scores in all 39 DM/PM patients. A varying frequency of measurements was above the upper limit of reference range with MHC having the highest percentage (60%, n=23) of abnormal results. Despite no clinical evidence for myocardial damage CKMB was increased in 51% (n=19), and cTnT was increased in 41% (n
Discussion
The determination of cardiac troponins, cTnT and cTnI, is a well-established method for the laboratory diagnosis of acute myocardial damage. Questions have been raised as to the specificity of cTnT for cardiac damage in patients with myopathies. Previous reports showed increased cTnT concentrations in patients with myopathies, even without other evidence for cardiac damage [11], [13]. The question, whether there is re-expression of fetal or adult isoforms of cTnT that gives rise to false
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2020, Thrombosis ResearchCitation Excerpt :We may not have been able to adequately distinguish cardiac myosin from SkM due to the high homology of the monoclonal antibody's recognition site [21]. However, plasma levels of cardiac myosin (<0.1 nmol/L) [31–35] are <1% of the average levels of SkM in plasma (4–20 nmol/L) [1,11,13]. Even when cardiac myosin levels are elevated as in the case of a myocardial infarction, it is <1 nmol/L [31–36].