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

Leffler, Jonatan LU ; Gullstrand, Birgitta LU ; Jönsen, Andreas LU ; Nilsson, Jan Åke LU ; Martin, Myriam LU ; Blom, Anna M. LU and Bengtsson, Anders A. LU (2013) In Arthritis Research and Therapy 15(4).
Abstract

Introduction: The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE). NETs consist of chromatin covered with antimicrobial enzymes and are normally degraded by DNase-I, an enzyme which is known to have reduced activity in SLE. Decreased ability to degrade NETs is associated with disease activity. In the current study we investigated how the ability of serum from SLE patients to degrade NETs varies during the course of SLE as well as what impact this may have for the clinical phenotype of SLE.Methods: Serum from 69 patients with SLE, included in a prospective study, was taken every 60 days for a median of 784 days. The ability of serum to degrade NETs was... (More)

Introduction: The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE). NETs consist of chromatin covered with antimicrobial enzymes and are normally degraded by DNase-I, an enzyme which is known to have reduced activity in SLE. Decreased ability to degrade NETs is associated with disease activity. In the current study we investigated how the ability of serum from SLE patients to degrade NETs varies during the course of SLE as well as what impact this may have for the clinical phenotype of SLE.Methods: Serum from 69 patients with SLE, included in a prospective study, was taken every 60 days for a median of 784 days. The ability of serum to degrade NETs was determined and associated with clinical parameters occurring before and at the time of sampling, as well as after sampling by using conditional logistic regression.Results: As many as 41% of all patients in the study showed decreased ability to degrade NETs at least once, but with a median of 20% of all time points. Decreased degradation was associated with manifestations of glomerulonephritis as well as low complement levels and elevated levels of antibodies directed against histones and DNA. Furthermore, the odds ratio for the patient to develop alopecia and fever after an episode of decreased NETs degradation was increased by four to five times compared to normal.Conclusions: Decreased degradation of NETs is associated with clinical manifestations in SLE and may contribute to disease pathogenesis. Potential therapeutics restoring the ability to degrade NETs could be beneficial for certain patients with SLE.

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organization
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Contribution to journal
publication status
published
subject
keywords
degradation, glomerulonephritis, neutrophil extracellular traps, prospective study, Systemic lupus erythematosus
in
Arthritis Research and Therapy
volume
15
issue
4
article number
R84
publisher
BioMed Central (BMC)
external identifiers
  • scopus:84893111758
  • pmid:23945056
ISSN
1478-6354
DOI
10.1186/ar4264
language
English
LU publication?
yes
id
04f0074a-5df1-474e-a7ed-46eecca1b004
date added to LUP
2019-05-23 09:42:37
date last changed
2020-09-23 07:42:52
@article{04f0074a-5df1-474e-a7ed-46eecca1b004,
  abstract     = {<p>Introduction: The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE). NETs consist of chromatin covered with antimicrobial enzymes and are normally degraded by DNase-I, an enzyme which is known to have reduced activity in SLE. Decreased ability to degrade NETs is associated with disease activity. In the current study we investigated how the ability of serum from SLE patients to degrade NETs varies during the course of SLE as well as what impact this may have for the clinical phenotype of SLE.Methods: Serum from 69 patients with SLE, included in a prospective study, was taken every 60 days for a median of 784 days. The ability of serum to degrade NETs was determined and associated with clinical parameters occurring before and at the time of sampling, as well as after sampling by using conditional logistic regression.Results: As many as 41% of all patients in the study showed decreased ability to degrade NETs at least once, but with a median of 20% of all time points. Decreased degradation was associated with manifestations of glomerulonephritis as well as low complement levels and elevated levels of antibodies directed against histones and DNA. Furthermore, the odds ratio for the patient to develop alopecia and fever after an episode of decreased NETs degradation was increased by four to five times compared to normal.Conclusions: Decreased degradation of NETs is associated with clinical manifestations in SLE and may contribute to disease pathogenesis. Potential therapeutics restoring the ability to degrade NETs could be beneficial for certain patients with SLE.</p>},
  author       = {Leffler, Jonatan and Gullstrand, Birgitta and Jönsen, Andreas and Nilsson, Jan Åke and Martin, Myriam and Blom, Anna M. and Bengtsson, Anders A.},
  issn         = {1478-6354},
  language     = {eng},
  month        = {08},
  number       = {4},
  publisher    = {BioMed Central (BMC)},
  series       = {Arthritis Research and Therapy},
  title        = {Degradation of neutrophil extracellular traps co-varies with disease activity in patients with systemic lupus erythematosus},
  url          = {http://dx.doi.org/10.1186/ar4264},
  doi          = {10.1186/ar4264},
  volume       = {15},
  year         = {2013},
}