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THU0055 Elevated Cfdna is Associated with Active Lupus Nephritis and May Mainly Derive from Netosis in Systemic Lupus Erythematosus
  1. S. Zhang,
  2. G. Wang,
  3. X. Lu
  1. Rheumatology, China-Japan Friendship Hospital, Beijing, China

Abstract

Background Abnormal formation and insufficient clearance of neutrophil extracellular traps (NETs) has been involved in lupus nephritis (LN). The residual NETs is one potential source of circulating cell-free DNA (cfDNA). However, whether elevated level of cfDNA could be related to LN and attributed to excessive formation and insufficient clearance of NETs are still unknown in systemic lupus erythematosus (SLE).

Objectives The present study tested the hypothesis that elevated level of cfDNA may be related to LN and stand for abnormal formation and degredation of NETs in SLE.

Methods Fifty four patients with SLE and 43 age- and sex-matched healthy controls were included in the study. cfDNA concentration was measured with Picogreen Kit, low-density granulocytes (LDGs) percentage in peripheral blood mononuclear cells (PBMCs) was tested by flow cytometer and DNase I activity was measured by radial enzyme-diffusion method.

Results cfDNA in SLE group was 236.66±40.09 ng/ml, significantly higher than that in healthy control group (187.96±40.55 ng/ml, P<0.0001). cfDNA in patients with LN was significantly higher than that in patients without LN (247.3±46.79 ng/ml vs. 213.6±31.34 ng/ml, P=0.0094). cfDNA in patients with active LN was significantly higher than that in patients with inactive LN (254.22±50.16 ng/ml vs. 215.93±29.10 ng/ml, P=0.0349). In SLE group, cfDNA positively correlated with quantitative 24-hour urinary protein (r=0.350, P=0.013), LDGs (r=0.6361, P=0.0019) and neutrophils (r=0.5990, P<0.0001), and reversely correlated with albumin (r=-0.500, P<0.0001) and endogenous creatinine clearance rate (Ccr) (r=-0.354, P=0.044). Compared to control group, SLE group exhibited a significantly increased percentage of LDGs in PBMCs and a significantly decreased DNase I activity.

Conclusions Our data suggests that elevated cfDNA is associated with active LN and may mainly derive from NETosis by neutrophils as well as LDGs in SLE. cfDNA could potentially aid in the prediction of LN risk in SLE patients.

References

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  3. Leffler J, Martin M, Gullstrand B, Tydén H, Lood C, Truedsson L. Neutrophil Extracellular Traps That Are Not Degraded in Systemic Lupus Erythematosus Activate Complement Exacerbating the Disease. J Immunol 2012; 188(7): 3522–31.

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Acknowledgements The authors would like to thank all participants.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.1956

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