The role of erythropoietin in Shiga toxin-mediated HUS

Infections with Shiga toxin-producing Escherichia coli (STEC) can cause a serious complication called hemolytic-uremic syndrome (HUS). In addition to acute kidney injury, this condition is characterized by a deficiency of platelets (thrombocytopenia) and microangiopathic hemolytic anemia (deficiency of red blood cells due to their destruction at thrombi in the smallest vessels). Erythropoietin (EPO) is a hormone that has a critical function in blood formation (hematopoiesis) and is used to treat various forms of anemia. HUS-mediated hemolytic anemia is not one of them so far. In addition to its known effect in hematopoiesis, EPO has become the focus of pharmacological research in recent decades, primarily because of its tissue-protective effects. In this context, tissue-protective peptide analogues that do not possess hematopoietic properties, such as pyroglutamate helix B surface peptide (pHBSP), have been synthesized.

Members of the NWG Translational Septomics (Head: Prof. Dr. med. Sina M. Coldewey, PhD) in cooperation with the research groups led by Prof. Diana Imhof (Bonn), Prof. Kerstin Amann and Prof. Christoph Daniel (Erlangen), Prof. Florian Gunzer (Dresden), Prof. Jan T. Kielstein (Braunschweig) and Prof. Isabel Hennig-Pauka (Hannover) investigated the role of EPO in Shiga toxin-mediated HUS in patient samples and various animal models of HUS.

The investigators demonstrated that endogenous EPO levels are uniformly elevated in HUS patients, pigs with STEC infections, and mice with Shiga toxin-induced HUS. Treatment of HUS mice with EPO or pHBSP reduces oxidative stress in the kidney and results in improved survival of the animals.

The findings were published in the journal Frontiers in Immunology. doi.org/10.3389/fimmu.2022.1010882