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

Leffler, Jonatan and Prohászka, Zoltán and Mikes, Bálint and Sinkovits, György and Ciacma, Katarzyna and Farkas, Péter and Réti, Marienn Györgyi and Kelen, Kata and Reusz, György and Szabó, Attila (2017) Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome. JOURNAL OF INNATE IMMUNITY, 9 (1). pp. 12-21. ISSN 1662-811X

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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 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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