Differential Detection of Skeletal Troponin I Isoforms in Serum of a Patient with Rhabdomyolysis: Markers of Muscle Injury?

Abstract

Unlike the extensive research devoted to the development of troponin-based diagnostic assays for myocardial disease, much less effort has been expended on the development of a counterpart for skeletal muscle disorders. The consensus that the cardiac troponins [cardiac troponin I (cTnI) and/or cTnT] should be used for diagnosis of myocardial infarction (MI), as well as for diagnosis and management of unstable angina, is based on their superior tissue specificity over such conventional markers as creatine kinase [(CK); see Refs. (1)(2)]. Although CK is the most common serum marker for skeletal muscle injury, it is not ideal for several reasons, including lack of tissue specificity, inability to reveal damage to specific skeletal fiber types (fast or slow), and inappropriately low values when glutathione concentrations are decreased because of liver or multiple-organ failure (3). Skeletal troponin I (sTnI), with its two distinct isoforms [fast (fsTnI) and slow (ssTnI)], like cTnI and cTnT, may have a similar advantage over conventional markers for detecting skeletal-muscle injury. In 1996, Rama et al. (4) described an experimental immunoenzymatic assay for sTnI using antibodies that cross-react with both sTnI and cTnI. The assumption of the investigators was that the concentrations of cTnI in patients with skeletal injury would be negligible. Others have since used this assay (5)(6)(7). For example, Onuoha et al. (7) found that serum sTnI reflects the severity and type of orthopedic and soft tissue injury. However, because this assay does not differentiate between the two isoforms of sTnI, which have a sequence homology of ∼56%, information about selective damage to particular fiber types is unavailable. Posttranslational modifications to the analyte, such as degradation, are also undetected by this assay. We applied our Western blot–direct serum analysis (WB-DSA) procedure (8), originally developed and successfully used for the detection …