Neutrophil activation in juvenile dermatomyositis: associations with muscle function and disease progression

Juvenile dermatomyositis (JDM) is an inflammatory vasculopathy characterized by muscle weakness and systemic inflammation. This study aimed to investigate the clinical utility of neutrophil activation markers, specifically calprotectin (S100A8/A9) and myeloperoxidase (MPO)-DNA complexes, as potential biomarkers for muscle inflammation and predictors of muscle outcomes in JDM.

Plasma levels of calprotectin and MPO-DNA were quantified using ELISA in JDM (n = 36), juvenile idiopathic arthritis (JIA, n = 13), and healthy controls (HCs, n = 21). Disease severity and muscle function were assessed using the Childhood Myositis Assessment Scale (CMAS), Physician Global Assessment (PGA), and Manual Muscle Testing 8 (MMT8). JDM patients exhibited significantly higher plasma calprotectin and MPO-DNA levels as compared to HCs (p = 0.0008 and p = 0.0048, respectively). Calprotectin levels correlated with muscle function scores (CMAS r=-0.682, p = 0.0002; MMT8 r=-0.59, p = 0.005; and PGA muscle scores r = 0.452, p = 0.014). Patients with elevated levels of both calprotectin and MPO-DNA tended to have greater disease activity and muscle involvement. Exploratory ROC analysis suggested that baseline calprotectin and MPO-DNA levels may help distinguish active disease. Notably, higher baseline levels of these markers correlated with improved MMT8 scores over time (r = 0.634, p = 0.027; r = 0.582, p = 0.047), suggesting an association with greater subsequent improvement in muscle strength.

These findings highlight calprotectin and MPO-DNA as potential biomarkers for JDM muscle inflammation and functional outcomes. These results suggest that neutrophil activation plays a key role in JDM pathogenesis and may provide insights into disease monitoring and treatment strategies.