Viruses in IBM Hit-and-run, hide and persist, or irrelevant?

Abstract

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-42, p62, and TDP43.(1,2) Proinflammatory cytokines enhance myocyte cell stress, which is specifically linked to amyloid-related protein misfolding.(1,3</SUP)