Z Gastroenterol 2013; 51 - K32
DOI: 10.1055/s-0033-1352672

Reduced expression of complement regulators CD55 and CD59 on peripheral blood cells is not involved in development of hemolytic uremic syndrome in patients with EHEC O104:H4 infection

W Dammermann 1, P Schipper 1, S Ullrich 2, K Fraedrich 1, J Schulze zur Wiesch 1, T Fründt 1, G Tiegs 3, A Lohse 1, S Lüth 1
  • 1I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • 2Institut für Anatomie und Exp. Morphologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
  • 3Institut für Experimentelle Immunologie und Hepatologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Aims: An outbreak of Shiga Toxin 2 (Stx-2) producing enterohemorrhagic E.coli (EHEC) O104:H4 infection in May 2011 caused enterocolitis and an unprecedented high 22% rate of hemolytic uremic syndrome (HUS). The monoclonal anti-C5 antibody Eculizumab (ECU) has been used experimentally in EHEC patients with HUS but treatment efficacy is uncertain. ECU can effectively prevent hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) caused by a lack of complement-regulating CD55 and CD59 on blood cells. We hypothesized a low expression of CD55 and CD59, as seen in atypical HUS in PNH, might correlate with HUS development in EHEC patients.

Methods: 76 EHEC patients (34: only gastrointestinal symptoms [GI], 23: HUS, 19: HUS and neurological symptoms[HUS/N]) and 12 healthy controls (HC) were tested for the expression of CD55 and CD59 on erythrocytes and leukocytes retrospectively. Additionally, the effect of Stx-2 on CD55 and CD59 expression on erythrocytes and leukocytes was studied ex vivo.

Results: CD55 expression on erythrocytes was similar in all patient groups and HC while CD59 showed a significantly higher expression in HUS and HUS/N patients compared to HC and the GI group. CD55 and CD59 expression on leukocytes and their subsets were significantly higher in all patient groups compared to HC regardless of ECU-treatment. However, CD59 expression was significantly higher in HUS and HUS/N patients treated combined with plasma separation (PS) and ECU compared to HC. Adding Stx-2 ex vivo had no effect on CD55 and CD59 expression on leukocytes from HC or patients.

Conclusion: HUS evolved independently from CD55 and CD59 expression on peripheral blood cells in EHEC O104:H4 infected patients. Our data point to a different mechanism within the complement system for HUS development in EHEC patients, when considering the original designated use of ECU to compensate protectively for the lack of CD55 and CD59 in PNH.