Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis

Aims Sporadic inclusion body myositis (s‐ IBM ) is characterized by rimmed vacuole formation and misfolded protein accumulation. Intracellular protein aggregates are cleared by autophagy. When autophagy is blocked aggregates accumulate, resulting in abnormal rimmed vacuole formation. This study investigated the autophagy–lysosome pathway contribution to rimmed vacuole accumulation. Methods Autophagy was studied in muscle biopsy specimens obtained from eleven s‐ IBM patients, one suspected hereditary IBM patient, nine patients with other inflammatory myopathies and nine non‐myopathic patients as controls. The analysis employed morphometric methods applied to immunohistochemistry using the endosome marker Clathrin, essential proteins of the autophagic cascade such as A u T opha G y‐related protein ATG5 , splicing variants of microtubule‐associated protein light chain 3a ( LC 3a) and LC 3b, compared with B eclin 1, the major autophagy regulator of both the initiation phase and late endosome/lysosome fusion of the autophagy–lysosome pathway. Results In muscle biopsies of s‐ IBM patients, an increased expression of C lathrin, ATG 5, LC 3a, LC 3b and B eclin 1 was shown. Moreover, the inflammatory components of the disease, essentially lymphocytes, were preferentially distributed around the B eclin 1 + myofibres. These affected myofibres also showed a moderate sarcoplasmic accumulation of SMI ‐31 + phospho‐tau paired helical filaments. Conclusion The overexpression of autophagy markers linked to the decreased clearance of misfolded proteins, including SMI ‐31, and rimmed vacuoles accumulation may exhaust cellular resources and lead to cell death.