Microparticle generation and leucocyte death in Shiga toxin-mediated HUS

Abstract

Background: Shiga toxin-induced haemolytic uraemic syndrome (STEC-HUS) is an acute multisystem disorder characterized by renal failure, neurological dysfunction, haemolysis and intravascular thrombosis. Circulating microparticles originating from a number of cell types including thrombocytes and leucocytes are elevated in paediatric patients. In vitro data also suggest modification of leucocyte death by Shiga toxin. Here, we investigated microparticle generation and leucocyte cell death in vivo in adult STEC-HUS patients during acute disease and recovery.

Methods: Multi-colour flow cytometry and immunofluorescence were used to assess microparticle concentration and provenience thrombocyte microparticle seeding to leucocytes and leucocyte cell death in adult STEC-HUS patients treated at a tertiary care centre during the STEC-HUS outbreak in Germany in 2011.

Results: Plasma microparticle concentrations of both platelet and leucocyte origin were elevated during acute STEC-HUS. Platelet microparticles (MP) were detected on a high proportion of monocytes and granulocytes. Among therapeutic interventions, plasma exchange reduced platelet marker expression on leucocytes, inhibition of complement had only moderate impact on the number of circulating MP and did not alter platelet microparticle binding to leucocytes. Numbers of apoptotic and necrotic monocytes and granulocytes were significantly increased in patients with STEC-HUS compared to healthy controls. Complement inhibition significantly increased the number of circulating apoptotic cells. Monocyte apoptosis on admission was significantly higher in patients subsequently assigned to plasma exchange or admitted to the intensive care unit.

Conclusions: In STEC-HUS, elevated numbers of circulating MP and dead leucocytes were detected. Monocyte and granulocyte deaths are novel markers of acute STEC-HUS that may actively contribute to tissue destruction by liberation of pro-inflammatory enzymes and cytokines.