title: Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Section of Medical Protein Chemistry, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors: Jonatan
authors: J
authors: Leffler
authors: Zoltán
authors: Z
authors: Prohászka
authors: Bálint
authors: B
authors: Mikes
authors: György
authors: G
authors: Sinkovits
authors: Katarzyna
authors: K
authors: Ciacma
authors: Péter
authors: P
authors: Farkas
authors: Marienn
authors: M
authors: Réti
authors: Kata
authors: K
authors: Kelen
authors: György S
authors: GS
authors: Reusz
authors: Attila J
authors: AJ
authors: Szabó
authors: Myriam
authors: M
authors: Martin
authors: Anna M
authors: AM
authors: Blom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003851:Deoxyribonucleases / Q000378:metabolism; D065206:Extracellular Traps / Q000378:metabolism*; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology*; D022621:Shiga Toxin / Q000276:immunology; D057049:Thrombotic Microangiopathies / Q000276:immunology*; D055815:Young Adult
chemical_list: D022621:Shiga Toxin; D003851:Deoxyribonucleases