Inhibition of terminal complement activation in severe Shiga toxin-associated HUS – perfect example for a fast track from bench to bedside

Typical haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy, leading to severe renal disease as well as life-threatening extrarenal complications. HUS is primarily caused by infections with enterohaemorrhagic Escherichia coli (EHEC) and 5–20% of EHEC infections result in HUS. EHEC bacteria produce several virulence factors, of which Shiga toxins are believed to play a central role. About 10% of all HUS cases are not caused by E. coli and are thus termed atypical HUS. These are observed as familial or sporadic forms and are most commonly caused by a dysregulation of the alternative pathway of the complement system due to inherited mutations of, or acquired autoantibodies against, complement regulator proteins. The, thereby, impaired control of complement, which plays a prominent role in the humoral immune system and in immune homeostasis, leads to a hyperactive state, including activation of endothelial cells and platelets, inflammation of small vessel and eventually to the