Natural killer cells are a potential source of oxidative stress in inclusion body myositis

Inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy in individuals over 50 years of age. IBM is considered a T cell-mediated disease. In contrast, the role of natural killer (NK) cells remains understudied. Here, we characterized the phenotype and function of peripheral NK cells in 22 IBM patients and 22 age-matched non-diseased controls. Flow cytometry revealed stable overall NK cell frequencies but a shift toward a more cytotoxic phenotype in IBM, with elevated NKG2D expression and increased granzyme A and B levels in CD56 ^dim NK cells. Functional assays demonstrated that NK cells from IBM patients exhibited enhanced cytotoxicity against primary human muscle cells. These findings suggest that NK cells may contribute to muscle fiber injury in IBM through NKG2D-driven cytotoxicity and reactive oxygen species generation. Our study highlights NK cells as potential amplifiers of inflammation and oxidative stress in IBM.