Inclusion body myositis: new insights into pathogenesis and therapeutic perspectives.

PURPOSE OF REVIEW: Inclusion body myositis (IBM) is the most common acquired myopathy in individuals over 50 years of age and remains refractory to conventional immunosuppressive therapies. This review summarizes recent advances in the understanding of IBM pathogenesis and highlights emerging therapeutic strategies. RECENT FINDINGS: Recent studies have refined the understanding of the interplay between degenerative and immune-mediated mechanisms in IBM. Abnormal protein aggregation, impaired proteostasis, and alterations of the autophagic pathway contribute to muscle fiber degeneration. In parallel, increasing evidence supports a central role for highly differentiated cytotoxic CD8+ T cells invading major histocompatibility complex class I-expressing muscle fibers. Recent immunophenotyping studies have identified expanded populations of terminally differentiated killer cell lectin-like receptor G1-expressing CD8+ T cells in blood and muscle, suggesting a potential role for these cells in sustaining chronic muscle injury. These findings have prompted the development of targeted immunotherapies aimed at selectively modulating pathogenic cytotoxic T-cell populations. SUMMARY: IBM appears to result from a complex interaction between degenerative and immune-mediated pathways. Improved characterization of the immune effector cells involved in muscle injury is opening new avenues for targeted therapies and may ultimately lead to treatments for this condition that currently lacks disease-modifying therapy.