calpain and Dermatomyositis

We present a girl with dermatomyositis, liver cysts and choroid plexus papilloma who was treated and followed for 7 years. Muscle histology revealed an inflammatory muscle disease and similar changes were detected in a brain tumor that was surgically removed at onset. Western blot analysis of the muscle revealed severely reduced calpain-3 protein. She was treated with pulse methylprednisolone treatment (800 mg i.v. for 4 days) followed by oral prednisone treatment (16 mg on alternate day) for 14 months, which improved muscle strength. Moreover, the cystic liver formations disappeared during steroid treatment. This is an unusual association of muscular disorder, steroid-responsive liver cysts, intracranial tumor and secondary calpain-3 deficiency. We speculate that this association is not coincidental, but mediated by an autoimmune attack against an antigen that is shared among the target tissues.

Topics: Antigens, CD; Calpain; Cerebral Ventricle Neoplasms; Child; Cysts; Dermatomyositis; Female; Humans; Liver Diseases; Magnetic Resonance Imaging; Muscle Proteins; Muscle, Skeletal; Paraneoplastic Syndromes; Ultrasonography

To clarify the significance of intracellular lysosomal (cathepsins B, L and H) and extralysosomal (calpain) proteolytic systems in the process of muscle fiber degradation in inflammatory myopathies, biopsied muscle specimens were examined from patients with polymyositis (PM) and dermatomyositis (DM). Generally, in specimens from patients with PM and DM, but not in those from normal controls, muscle fibers surrounding inflammatory infiltrates or in the perifascicular regions, and occasionally mononuclear cell infiltrates demonstrated positive immunostaining for calpain and cathepsins B, L, and H. In addition, enzyme activities of cathepsins B and L increased in specimens with inflammatory myopathy. These results suggest that calpain and cathepsins play a significant role in the process of muscle fiber destruction in inflammatory myopathy.

Topics: Adult; Atrophy; Biopsy; Calpain; Cathepsin B; Cathepsin H; Cathepsin L; Cathepsins; Cysteine Endopeptidases; Dermatomyositis; Endopeptidases; Female; Humans; Inflammation; Lysosomes; Male; Middle Aged; Muscle Fibers, Skeletal; Muscle, Skeletal; Necrosis; Polymyositis