Session Information
Title: Systemic Lupus Erythematosus - Clinical Aspects I - Renal, Malignancy, Cardiovascular Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: Insufficient clearance of neutrophil extracellular traps (NETs) has been involved in lupus nephritis and can cause the increase of residual NETs in vivo, which is considered to be one main source of circulating cell-free DNA (cfDNA). However, whether elevated level of cfDNA could be attributed to excessive formation and insufficient clearance of NETs is still unknown in SLE. This study focused on it and explored whether cfDNA could be a biomarker for organ involvement related to abnormal formation and degradation 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, percentage of low-density granulocytes (LDGs) in peripheral blood mononuclear cells (PBMCs) was tested by flow cytometer and DNaseⅠactivity was measured by radial enzyme-diffusion method. Linear correlation analysis were performed between these three, SLE disease activity index (SLEDAI) and other serological parameters. Multiple linear regression was performed to identify the influencing factor of cfDNA.
Results: cfDNA in SLE group was 239.76±57.15 ng/ml, significantly higher than that in healthy control group (187.96±40.55 ng/ml, P<0.0001). DNaseⅠactivity in SLE group was 0.26±0.17 U/ml, significantly lower than that in healthy control group (0.43±0.26 U/ml, P<0.0001). Percentage of LDGs in PBMCs of SLE group was 8.29%±12.86%, significantly higher than that in healthy controls group (1.15%±0.71%, P=0.0036). In SLE group, cfDNA positively correlated with percentage of LDGs in PBMCs (r=0.651, P=0.002), neutrophils (r=0.584, P<0.0001), ESR (r=0.364, P=0.007), CRP (r=0.291, P=0.032) and urine protein (r=0.350, P=0.013) and reversely correlated with albumin (r=-0.500, P<0.0001) and Ccr (r=-0.354, P=0.044). Multiple linear regression indicated that plasma albumin and neutrophils can explain 38.2% of elevated cfDNA in SLE patients.
Conclusion: The elevated level of cfDNA may mainly derive from NETosis of common neutrophils as well as LDGs and is associated with lupus nephritis severity.
Disclosure:
S. Zhang,
None;
G. Wang,
None;
X. Lu,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-level-of-cfdna-mainly-derive-from-netosis-of-common-neutrophils-as-well-as-low-density-granulocytes-in-systemic-lupus-erythematosus-and-is-associated-with-lupus-nephritis-severity/