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

Moore, Stanley ; Juo, Hsin Hsuan ; Nielsen, Christoffer T. ; Tyden, Helena LU ; Bengtsson, Anders A. LU and Lood, Christian LU (2020) In The Journal of rheumatology 47(11). p.1652-1660
Abstract

OBJECTIVE: Neutrophil 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. METHODS: Levels 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. RESULTS:... (More)

OBJECTIVE: Neutrophil 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. METHODS: Levels 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. RESULTS: Patients 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). CONCLUSION: NET 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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cardiovascular disease, nephritis, neutrophil extracellular trap, systemic lupus erythematosus
in
The Journal of rheumatology
volume
47
issue
11
pages
9 pages
publisher
Journal of Rheumatology Publishing Company Limited
external identifiers
  • scopus:85095461724
  • pmid:31839592
ISSN
0315-162X
DOI
10.3899/jrheum.190875
language
English
LU publication?
yes
id
62c1783c-cf5a-41b8-9bb8-436bfa943e49
date added to LUP
2020-11-16 07:34:10
date last changed
2024-08-23 05:46:53
@article{62c1783c-cf5a-41b8-9bb8-436bfa943e49,
  abstract     = {{<p>OBJECTIVE: Neutrophil 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. METHODS: Levels 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. RESULTS: Patients with SLE had elevated levels of NET in circulation compared to healthy controls (p &lt; 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p &lt; 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 &lt; 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p &lt; 0.001). CONCLUSION: NET 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.</p>}},
  author       = {{Moore, Stanley and Juo, Hsin Hsuan and Nielsen, Christoffer T. and Tyden, Helena and Bengtsson, Anders A. and Lood, Christian}},
  issn         = {{0315-162X}},
  keywords     = {{cardiovascular disease; nephritis; neutrophil extracellular trap; systemic lupus erythematosus}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1652--1660}},
  publisher    = {{Journal of Rheumatology Publishing Company Limited}},
  series       = {{The Journal of rheumatology}},
  title        = {{Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus}},
  url          = {{http://dx.doi.org/10.3899/jrheum.190875}},
  doi          = {{10.3899/jrheum.190875}},
  volume       = {{47}},
  year         = {{2020}},
}