Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in childhood. The disease is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS has various etiological factors, however most cases of HUS are associated with Shiga toxin (Stx)- producing enterohemorrhagic Escherichia coli (EHEC) infections. This type of HUS, also known as eHUS, is a disease which affects only 5-15% of human beings after an infection with EHEC bacteria; it has therefore being regarded as opportunistic complication of an EHEC infection, although the molecular bases originating in host defence that are facilitating severe disease are not known yet.
One of the main virulence factors is the produced Shiga toxin, especially Stx2a. Recently two forms of the toxin that act in different pathophysiological stages have been described. On the host side, the most important host factor associated with the development of the disease is complement system. Allotypes of complement regulatory proteins have already been found to be associated with eHUS, and complement inhibiting therapy is used in eHUS cases.
Our group proposes a multidisciplinary approach to elucidate the interaction of both Stx2a forms with complement. At the same time, we are trying to understand how other factors of the host as gender, age, immune status or the presence of iron, affect the course of the disease. Investigation into these aspects of HUS may prove helpful in developing new interventions for improving clinical outcomes in affected patients.
