scholarly journals Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus

2013 ◽  
Vol 15 (4) ◽  
pp. R84 ◽  
Author(s):  
Jonatan Leffler ◽  
Birgitta Gullstrand ◽  
Andreas Jönsen ◽  
Jan-Åke Nilsson ◽  
Myriam Martin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps

scholarly journals Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus

2019 ◽  
Vol 47 (11) ◽  
pp. 1652-1660 ◽  
Author(s):  
Stanley Moore ◽  
Hsin-Hsuan Juo ◽  
Christoffer T. Nielsen ◽  
Helena Tyden ◽  
Anders A. Bengtsson ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
At Risk ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Severe Disease ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Patients At Risk

ObjectiveNeutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity.MethodsLevels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44–142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system.ResultsPatients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001).ConclusionNET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.

scholarly journals The enrichment of neutrophil extracellular traps impair the placentas of systemic lupus erythematosus through accumulating decidual NK cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meng Jiang ◽  
Nan Shen ◽  
Haibo Zhou ◽  
You Wang ◽  
Sihan Lin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Nk Cells ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Clinical Samples ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Fetal Birth Weight ◽  
Immunological Disorder ◽  
Adverse Pregnancy

AbstractDespite the advances made in the management of pregnancies in women with systemic lupus erythematosus (SLE), the rate of adverse pregnancy outcomes is still higher than that in the general population. In the last few years, neutrophil extracellular traps (NETs) were proven to be detrimental in both autoimmune diseases and placental injury. We investigated whether NETs could be detected in the placentas of pregnant individuals with SLE and explored the relationship between NETs and decidual natural killer cells (dNKs), which comprise the majority of immune cells at the maternal–fetal interface, using clinical samples and animal models. In this study, we found that the infiltration of NETs and dNKs, especially CD56+CD16+ NK cells, was significantly increased in pregnant individuals with SLE with placental insufficiency. In the murine models of SLE, the number of dNKs was significantly decreased due to the decreased formation of NETs affected by Ly6G. Moreover, the histopathological placental injury was reduced, with a remarkable increase in fetal birth weight. This study shows that NETs may contribute to immunological disorder in the placenta and the pathological changes in pregnancies with SLE, which provides a research basis for further explorations of the mechanism of SLE in placental impairment.

Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus

2019 ◽  
Vol 39 (11) ◽  
pp. 1849-1857 ◽  
Author(s):  
Ivica Jeremic ◽  
Olivera Djuric ◽  
Milos Nikolic ◽  
Marina Vlajnic ◽  
Aleksandra Nikolic ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps

scholarly journals SP043AUTOPHAGY-MEDIATED DELIVERY OF TISSUE FACTOR ON NEUTROPHIL EXTRACELLULAR TRAPS BY MAY PROMOTE KIDNEY INJURY IN SYSTEMIC LUPUS ERYTHEMATOSUS

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii394-iii395
Author(s):  
Eleni A Frangou ◽  
Konstantinos Kambas ◽  
George Bertsias ◽  
Panayotis Verginis ◽  
Konstantinos Ritis ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Tissue Factor ◽  
Lupus Erythematosus ◽  
Kidney Injury ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps

scholarly journals POS0108 PLASMA MITOCHONDRIAL DNA AS A BIOMARKER IN DIAGNOSIS AND FOLLOW-UP OF SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 265.1-265
Author(s):  
S. Giaglis ◽  
D. Daoudlarian ◽  
D. Kyburz ◽  
N. Venhoff ◽  
U. Walker
Keyword(s):  
Mitochondrial Dna ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Operating Characteristic ◽  
Neutrophil Extracellular Traps ◽  
Healthy Individuals ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Copy Numbers

Background:A fundamental role of mitochondria in systemic lupus erythematosus (SLE) was recently demonstrated (1). In brief, mitochondrial ROS participate in the formation of neutrophil extracellular traps (NETs) (2), while extrusion of cell-free mitochondria and highly oxidized interferogenic mtDNA causes disease in an animal model of SLE (3-5).Objectives:The diagnostic and prognostic value of cell-free DNA in SLE is still unknown. The aim of the present study was therefore to examine the clinical utility of cell-free DNA quantification as a non-invasive biomarker in SLE.Methods:Total DNA was isolated from platelet-free plasma samples of healthy individuals (HC) and consecutive SLE patients. Plasma and clinical data were collected at baseline and follow-up. Copy numbers were quantified by qPCR for mitochondrial (mt) DNA (ATP-6 gene) and nuclear (n) DNA (GAPDH gene).Results:Fifty-six HC (median age 48.3 ± 13.5, 64% female) and 103 SLE patients (median age 46.8 ± 15.8, 99% female, mean SLEDAI: 3 ± 4) were available for analysis.mtDNA levels were significantly elevated in SLE plasma (1.3x108 copies/ml plasma, 95% CI: 7.3x107 to 1.7 x108)), compared to HC plasma (8.6x106 copies/ml plasma, 95% CI: 6.9x106 to 1.0x107, p<0.0001). nDNA levels in contrast did not differ between SLE (8.3x106 copies/ml plasma, 95%CI: 5.9x106 to 1.4 x107) and HC (1.0x107 copies/ml plasma, 95%CI: 2.0x106 to 1.5 x107, p=0.61). Receiver operating characteristic curve analysis showed that a cut-off value of 1.9x107 mtDNA copy numbers differentiated between SLE and HC with 87.4% sensitivity, 94.6% specificity and an AUC of 0.95 (Figure 1a).mtDNA levels correlated with the SLE Disease Activity Index 2000 (SLEDAI-2K) (r=0.29, p=0.0026), less so also nDNA copy numbers (r=0.24, p=0.014). There was no association of mtDNA elevation with any particular type of SLE organ involvement and no correlation between mtDNA copy numbers in SLE plasma and dsDNA antibody levels.Follow-up data were available for 32 SLE patients (median follow-up 4.0 months, IQR: 4.0). delta mtDNA-levels robustly correlated with changes in SLEDAI-2K (r=0.51, p=0.0012, Figure 1b).Conclusion:The quantification of cell free mtDNA, but not nDNA copy numbers allows a sensitive and specific distinction between healthy individuals and patients with SLE. mtDNA levels correlate cross sectionally with disease activity in SLE patients and within individual SLE patients longitudinally with the SLEDAI. Plasma mtDNA quantification may therefore aid in the diagnosis of SLE and in monitoring SLE activity.References:[1]Riley JS, Tait SW. Mitochondrial DNA in inflammation and immunity. EMBO Rep. 2020;21(4):e49799.[2]West AP, Shadel GS. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol. 2017;17(6):363-75.[3]Crow MK, Olferiev M, Kirou KA. Type I Interferons in Autoimmune Disease. Annu Rev Pathol. 2019;14:369-93.[4]Kim J, Gupta R, Blanco LP, Yang S, Shteinfer-Kuzmine A, Wang K, et al. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science. 2019;366(6472):1531-6.[5]Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat Med. 2016;22(2):146-53.Declaration of conflict of interest:UW is coinventor of patents owned by Freiburg University; NV is coinventor of patents owned by Freiburg University.Figure 1.(a) Receiver operating characteristic curve for mtDNA plasma concentrations to discriminate between HC and SLE patients. AUC: area under the curve. (b) Changes in plasma mtDNA levels in SLE patients correlate with the evolution of disease activity at follow-up.Disclosure of Interests:None declared

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