Immune and myodegenerative pathomechanisms in inclusion body myositis.
Christian W KellerJens SchmidtJan D LünemannPublished in: Annals of clinical and translational neurology (2017)
Inclusion Body Myositis (IBM) is a relatively common acquired inflammatory myopathy in patients above 50 years of age. Pathological hallmarks of IBM are intramyofiber protein inclusions and endomysial inflammation, indicating that both myodegenerative and inflammatory mechanisms contribute to its pathogenesis. Impaired protein degradation by the autophagic machinery, which regulates innate and adaptive immune responses, in skeletal muscle fibers has recently been identified as a potential key pathomechanism in IBM. Immunotherapies, which are successfully used for treating other inflammatory myopathies lack efficacy in IBM and so far no effective treatment is available. Thus, a better understanding of the mechanistic pathways underlying progressive muscle weakness and atrophy in IBM is crucial in identifying novel promising targets for therapeutic intervention. Here, we discuss recent insights into the pathomechanistic network of mutually dependent inflammatory and degenerative events during IBM.
Keyphrases
- oxidative stress
- immune response
- skeletal muscle
- randomized controlled trial
- ejection fraction
- end stage renal disease
- multiple sclerosis
- newly diagnosed
- interstitial lung disease
- cell death
- prognostic factors
- toll like receptor
- late onset
- dendritic cells
- systemic sclerosis
- amino acid
- early onset
- inflammatory response
- combination therapy
- patient reported outcomes
- climate change
- muscular dystrophy