Diagnosis, pathogenesis and treatment of inclusion body myositis

We provide an update of progress gained from research into sporadic inclusion body myositis (s-IBM).

Most research on s-IBM has focused on the inflammatory reaction or the accumulation of pathological proteins in vacuolated muscle fibres. The inflammatory reaction is characterized by clonal expansions of lymphocytes, predominantly CD8 cytotoxic T cells, which invade and destroy muscle fibres. That costimulatory molecules have been identified demonstrates that muscle fibres can act as antigen presenting cells, and the expression of various chemokines in muscle indicates their importance in the immunopathogenesis of s-IBM. The region of interest for a susceptibility gene in the major histocompatibility complex has been narrowed, and for the first time it has been demonstrated that a chronic viral infection can trigger the inflammatory process leading to s-IBM. The nature of the accumulated material associated with the vacuoles has been extensively investigated over the past few years. Amyloid-beta and phosphorylated tau protein in intracellular inclusions are a characteristic finding in s-IBM, which may lead to calcium dyshomeostasis and endoplasmic reticulum stress. The proteasomal system is upregulated, including immunoproteasomes. 'Molecular misreading' leading to ubiquitin mRNA mutations and accumulation of pathological ubiquitin in muscle fibres may be associated with proteasomal dysfunction. There is still no efficient treatment for s-IBM, but the effects of new, more specific immunotherapies have begun to be explored.

Recent findings indicate that both inflammatory reaction and abnormal protein accumulation are important for the pathogenesis in s-IBM. The link between them continues to await elucidation.