Core Clinical Laboratory Services Division, Department of Laboratory Medicine and Pathology, Mayo Clinic and Medical School, Rochester, Minnesota 55905, USA.
J Am Coll Cardiol. 2011 Oct 18;58(17):1819-24. doi: 10.1016/j.jacc.2011.08.026. Epub 2011 Sep 29.
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.
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.
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.
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.
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.
本研究旨在确定病变骨骼肌中是否存在免疫反应性心肌肌钙蛋白 T（cTnT）表达，这种情况可能导致 cTnT 出现假阳性升高。
心肌肌钙蛋白（I 或 T）是诊断心脏损伤的首选生物标志物。最近，我们遇到了一个挑战 cTnT 特异性的病例。
在 Mayo 诊所神经肌肉诊所就诊的肌病患者中筛选 cTnT 升高。如果升高，则进行 cTnI 检测。如果正常，则获取骨骼肌活检组织，使用第四代和高敏 cTnT 检测试剂盒的捕获和检测抗体进行 Western blot 分析。结果与正常心脏组织的发现进行比较。
16 例患者 cTnT 升高但 cTnI 正常。所有患者均经临床评估、临床检查和活检诊断为肌病。获得了 4 份剩余活检样本。所有 3 种用于 cTnT（M11.7、M7）和高敏 cTnT（5D8、M7）检测的抗体在 4 例病变骨骼肌活检标本和心脏组织中与 37-39kDa 蛋白均具有免疫反应性。还在 1 例患者中发现了第二种免疫反应性同工型（34 至 36kDa）。所有非心脏对照组织均未表达免疫反应性蛋白。
这些结果表明，病变骨骼肌中存在可能导致循环 cTnT 水平升高的形式。这些增加可能反映了重新表达的同工型。临床医生需要意识到，当存在骨骼肌病理时，非心脏性 cTnT 增加可能会导致可能的心脏损伤的假阳性诊断。
