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Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome

Leffler, Jonatan LU ; Prohászka, Zoltán; Mikes, Bálint; Sinkovits, György; Ciacma, Katarzyna LU ; Farkas, Péter; Réti, Marienn; Kelen, Kata; Reusz, György S. and Szabó, Attila J., et al. (2017) In Journal of Innate Immunity 9(1). p.12-21
Abstract

Background: Neutrophil extracellular traps (NETs) can stimulate thrombosis, and their degradation is decreased in several autoimmune disorders. It was recently reported that some patients with haemolytic uraemic syndrome (HUS) also fail to degrade NETs and that neutrophils from Shiga toxin-associated HUS are primed to form NETs. Method: We used a well-characterized cohort of 74 thrombotic microangiopathy (TMA) patients, with a subset also providing follow-up samples, and 112 age-matched controls to investigate NET degradation and serum nuclease activity in TMA before, during and after treatment. Results: We identified that in the cohort of TMA patients, 50% of patients with Shiga toxin-associated HUS displayed a decreased ability to... (More)

Background: Neutrophil extracellular traps (NETs) can stimulate thrombosis, and their degradation is decreased in several autoimmune disorders. It was recently reported that some patients with haemolytic uraemic syndrome (HUS) also fail to degrade NETs and that neutrophils from Shiga toxin-associated HUS are primed to form NETs. Method: We used a well-characterized cohort of 74 thrombotic microangiopathy (TMA) patients, with a subset also providing follow-up samples, and 112 age-matched controls to investigate NET degradation and serum nuclease activity in TMA before, during and after treatment. Results: We identified that in the cohort of TMA patients, 50% of patients with Shiga toxin-associated HUS displayed a decreased ability to degrade NETs. NET degradation correlated with serum nuclease activity, but not with autoantibodies against double-stranded DNA, which has been previously observed in some autoimmune disorders. Further, NET degradation negatively correlated with serum creatinine levels, suggesting that kidney function was negatively impacted by the low NET degradation ability. Conclusions: We revealed that decreased NET degradation is a common feature of Shiga toxin-associated HUS and that it is associated with decreased kidney function in these patients. It remains to be clarified whether improving NET degradation would be beneficial for the patient.

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publication status
published
subject
keywords
Degradation, Kidney injury, Neutrophil extracellular traps, Nuclease activity, Shiga toxin-associated haemolytic uraemic syndrome, Thrombotic microangiopathies
in
Journal of Innate Immunity
volume
9
issue
1
pages
12 - 21
publisher
Karger
external identifiers
  • scopus:84992694408
  • wos:000392166700003
ISSN
1662-811X
DOI
10.1159/000450609
language
English
LU publication?
yes
id
0237348b-0c82-4c6c-8108-2f8e220f59c5
date added to LUP
2016-11-14 12:23:32
date last changed
2018-10-21 04:40:40
@article{0237348b-0c82-4c6c-8108-2f8e220f59c5,
  abstract     = {<p>Background: Neutrophil extracellular traps (NETs) can stimulate thrombosis, and their degradation is decreased in several autoimmune disorders. It was recently reported that some patients with haemolytic uraemic syndrome (HUS) also fail to degrade NETs and that neutrophils from Shiga toxin-associated HUS are primed to form NETs. Method: We used a well-characterized cohort of 74 thrombotic microangiopathy (TMA) patients, with a subset also providing follow-up samples, and 112 age-matched controls to investigate NET degradation and serum nuclease activity in TMA before, during and after treatment. Results: We identified that in the cohort of TMA patients, 50% of patients with Shiga toxin-associated HUS displayed a decreased ability to degrade NETs. NET degradation correlated with serum nuclease activity, but not with autoantibodies against double-stranded DNA, which has been previously observed in some autoimmune disorders. Further, NET degradation negatively correlated with serum creatinine levels, suggesting that kidney function was negatively impacted by the low NET degradation ability. Conclusions: We revealed that decreased NET degradation is a common feature of Shiga toxin-associated HUS and that it is associated with decreased kidney function in these patients. It remains to be clarified whether improving NET degradation would be beneficial for the patient.</p>},
  author       = {Leffler, Jonatan and Prohászka, Zoltán and Mikes, Bálint and Sinkovits, György and Ciacma, Katarzyna and Farkas, Péter and Réti, Marienn and Kelen, Kata and Reusz, György S. and Szabó, Attila J. and Martin, Myriam and Blom, Anna M.},
  issn         = {1662-811X},
  keyword      = {Degradation,Kidney injury,Neutrophil extracellular traps,Nuclease activity,Shiga toxin-associated haemolytic uraemic syndrome,Thrombotic microangiopathies},
  language     = {eng},
  number       = {1},
  pages        = {12--21},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome},
  url          = {http://dx.doi.org/10.1159/000450609},
  volume       = {9},
  year         = {2017},
}