These authors contributed equally to this work. Both are corresponding authors.
Enhanced formation and impaired degradation of neutrophil extracellular traps in dermatomyositis and polymyositis: a potential contributor to interstitial lung disease complications
Version of Record online: 9 JUN 2014
© 2014 British Society for Immunology
Clinical & Experimental Immunology
Volume 177, Issue 1, pages 134–141, July 2014
How to Cite
Zhang, S., Shu, X., Tian, X., Chen, F., Lu, X. and Wang, G. (2014), Enhanced formation and impaired degradation of neutrophil extracellular traps in dermatomyositis and polymyositis: a potential contributor to interstitial lung disease complications. Clinical & Experimental Immunology, 177: 134–141. doi: 10.1111/cei.12319
- Issue online: 9 JUN 2014
- Version of Record online: 9 JUN 2014
- Accepted manuscript online: 11 MAR 2014 01:39AM EST
- Manuscript Accepted: 5 MAR 2014
- General Program of the National Natural Science Foundation of China. Grant Number: 81172860
- Beijing Science and Technology Committee. Grant Number: Z111107058811084
Dermatomyositis (DM) and polymyosits (PM) are systemic autoimmune diseases whose pathogeneses remain unclear. Neutrophil extracellular traps (NETs) are reputed to play an important role in the pathogenesis of autoimmune diseases. This study tests the hypothesis that NETs 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 NETs. Plasma DNase I activity was tested to further explore possible reasons for the incomplete degradation of NETs. 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 (cfDNA) in DM/PM. NETs degradation and DNase I activity were also decreased significantly in DM/PM patients and were correlated positively. Moreover, DM/PM patients with ILD exhibited the lowest NETs degradation in vitro due to the decrease in DNase I activity. DNase I activity in patients with anti-Jo-1 antibodies was significantly lower than in patients without. Glucocorticoid therapy seems to improve DNase I activity. Our findings demonstrate that excessively formed NETs cannot be degraded completely because of decreased DNase 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.