Background Dermatomyositis (DM) and polymyosits (PM) are systemic autoimmune diseases with ambiguous pathogenesis. Neutrophil extracellular traps (NETs) is considered to play an important role in pathogenesis of autoimmune disease.
Objectives The present study tested the hypothesis that NETs may be pathogenic in DM/PM.
Methods Plasma samples from 97 DM/PM patients (72DM, 25PM) and 54 healthy controls were tested for formation and degradation of NETs. Plasma DNase I activity was tested to further analyze the reason for abnormal degradation of NETs. Results from thirty five DM patients and seven PM patients with ILD were compared with DM/PM patients without ILD.
Results Compared with Control, DM/PM exhibited a significantly enhanced NETs formation (191.6±52.88 RFUs vs. 246±93.48 RFUs, P=0.002), which was supported by elevated level of plasma LL-37 and cfDNA in DM/PM. DM/PM also exhibited a significantly decreased ability to degrade NETs and DNase I activity. The percentage of NETs degraded by plasma significantly correlated with plasma DNase I activity in DM/PM. Moreover, DM/PM patients with ILD exhibited a significantly lower ability to degrade NETs and DNase I activity than patients without. DNase I activity in patients with anti-Jo-1 antibodies was significantly lower than that in patients with negative anti-Jo-1 antibodies. Glucocorticoids therapy seems to improve the activity of DNase I.
Conclusions The collective evidence demonstrated that the excessively formed NETs cannot be completely degraded owing to impairment of DNase I activity in DM/PM, especially in DML/PML, suggesting that residual NETs may participate in pathogenesis of ILD and DNase I may be a potential target.
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Acknowledgements The authors thank all patients and volunteers who participated in this study.
Disclosure of Interest None declared