Enhanced formation and impaired degradation of neutrophil extracellular traps in dermatomyositis and polymyositis: a potential contributor to interstitial lung disease complications

Summary Dermatomyositis ( DM ) and polymyosits ( PM ) are systemic autoimmune diseases whose pathogeneses remain unclear. Neutrophil extracellular traps ( NET s) are reputed to play an important role in the pathogenesis of autoimmune diseases. This study tests the hypothesis that NET s may be pathogenic in DM / PM . Plasma samples from 97 DM / PM patients (72 DM , 25 PM ) and 54 healthy controls were tested for the capacities to induce and degrade NET s. Plasma DN ase I activity was tested to further explore possible reasons for the incomplete degradation of NET s. Results from 35 DM patients and seven PM patients with interstitial lung disease ( ILD ) were compared with results from DM / PM patients without ILD . Compared with control subjects, DM / PM patients exhibited a significantly enhanced capacity for inducing NETs , which was supported by elevated levels of plasma LL ‐37 and circulating cell‐free DNA (cf DNA ) in DM / PM . NET s degradation and DN ase I activity were also decreased significantly in DM / PM patients and were correlated positively. Moreover, DM / PM patients with ILD exhibited the lowest NET s degradation in vitro due to the decrease in DN ase I activity. DN ase I activity in patients with anti‐ J o‐1 antibodies was significantly lower than in patients without. Glucocorticoid therapy seems to improve DN ase I activity. Our findings demonstrate that excessively formed NET s cannot be degraded completely because of decreased DN ase I activity in DM / PM patients, especially in patients with ILD , suggesting that abnormal regulation of NETs may be involved in the pathogenesis of DM / PM and could be one of the factors that initiate and aggravate ILD .