Chaperones in sporadic inclusion body myositis-Validation of proteomic data.

INTRODUCTION:Sporadic inclusion body myositis (sIBM) is characterized by myopathological features including rimmed vacuoles (RVs) and proteins associated with protein aggregation, autophagy, and inflammation. Previous proteomic studies of RV areas revealed an overrepresentation of several chaperones and subunits of the T-complex protein 1 (TCP-1), which is involved in prevention of protein aggregation. METHODS:To validate our proteomic findings, immunofluorescence analyses of selected chaperones and quantitative Western blot analysis of TCP-1 proteins were performed in five sIBM patients and five healthy controls. RESULTS:Immunofluorescence studies confirmed increased immunoreactivity for VCP, UNC45B, GRP-75, αB-crystallin, LAMP-2, Rab-7a, and TCP-1α and TCP-θ in RVs. Quantitative Western blot analysis revealed a significantly higher level of TCP-1 in sIBM muscle tissue when compared with healthy controls. DISCUSSION:Our study findings validate new insights in protein quality control and degradation processes that seem to be relevant in sIBM. These data provide an important basis for future functional and therapeutic studies.