Viruses in IBM

Inclusion body myositis (IBM) is the most common and disabling inflammatory myopathy above age 50 years, with seemingly increasing prevalence and complex pathogenesis.1,2 Cytotoxic-perforin-secreting CD8+ cells clonally expand in situ, invading healthy-appearing major histocompatibility complex class I–expressing muscle fibers; cytokines, costimulatory, and adhesion molecules are upregulated; and B cells are expanded with antibody production. Degenerative features are concurrently prominent, highlighted by autophagic vacuoles and accumulation of misfolded proteins, such as amyloid precursor protein, amyloid-β42, p62, and TDP43.1,2 Proinflammatory cytokines enhance myocyte cell stress, which is specifically linked to amyloid-related protein misfolding.1,3