AB0207 Enhanced Formation and Impaired Degradation of Neutrophil Extracellular TRAPS in Dermatomyositis and Polymyositis: A Potential Contributor to Dm/Pm- Complicated Ild

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.

References

Lundberg IE. Pathogenesis, classification and treatment of inflammatory myopathies. Nat Rev Rheumatol 2011;7:297–306 Danoff SK, Casciola-Rosen L. The lung as a possible target for the immune reaction in myositis. Arthritis Research & Therapy 2011;13:230. Cheng OZ, Palaniyar N. NET balancing: a problem in inflammatory lung diseases. Front Immunol 2013;4:1. Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs Are a Source of Citrullinated Autoantigens and Stimulate Inflammatory Responses in Rheumatoid Arthritis. Sci Transl Med 2013 Mar 27;5(178):178ra40. Keshari RS, Jyoti A, Dubey M, Kothari N, Kohli M, Bogra J, Barthwal MK, Dikshit M. Cytokines Induced Neutrophil Extracellular Traps Formation: Implication for the Inflammatory Disease Condition. PLoS ONE 2012;7(10): e48111.

Acknowledgements

The authors thank all patients and volunteers who participated in this study.

Disclosure of Interest

None declared

DOI

10.1136/annrheumdis-2014-eular.2472