Enhanced systemic oxidative stress response in patients with idiopathic inflammatory myopathies

Abstract

Idiopathic inflammatory myopathies (IIM) are characterized by chronic inflammation, endothelial dysfunction, and muscle tissue mitochondrial defect, leading to the local oxidative stress response. However, data on its systemic intensity and correlation with IIM clinical and laboratory characteristics remains scarce. In clinically stable dermatomyositis (n = 18) and myositis (n = 38) patients and matched controls (n = 50), we measured global oxidative stress response in peripheral blood using a novel coumarin boronic acid (CBA) assay enabling real-time detection of protein hydroperoxides (HP) formed in serum. We documented 36% faster kinetics (p < 0.001) and a 68% increase in the cumulative (p = 0.003) fluorescent product generation in the IIM group compared to the control, which indicates higher HP formation associated with systemic oxidative stress. The dynamics of fluorescent product growth were similar in the dermatomyositis and myositis groups. Interestingly, myositis patients with a marked increase in HP formation were characterized by lower serum myoglobin levels (p = 0.038). There was also an inverse correlation between serum myoglobin and the kinetics of HP formation (e.g., for cumulative in-time generation r = –0.35, p = 0.03). The systemic oxidative stress response measures were not related to clinical characteristics of the disease and treatment, internal medicine comorbidities, smoking status, or autoantibody profile. IIM are characterized by a global pro-oxidant imbalance reflected by enhanced HP generation in serum. Furthermore, muscle weakening without active signs of muscle damage may be related to the increased local and systemic oxidative stress response, suggesting non-inflammatory pathomechanism of the disease that our technically undemanding assay may evaluate.