Changes in tissue expression of coagulation-related molecules after challenge with coagulopathic Shiga toxin-2
Thompson, Morgan Paige
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Typical Hemolytic Uremic Syndrome (HUS) presents as a complication of infection with Shiga-toxin producing E. coli (STEC). While there are many animal models for infection, few show true signs of HUS. Additionally, these models differ greatly from the clinical presentation that affects small children and elderly populations. Immunohistochemical assays of tissues from a known HUS model may provide insight into molecular changes associated with the condition, particularly as it pertains to clotting factors. In this study, tissue factor (TF) was investigated in the kidneys of non-human primates previously injected with Shiga-Toxin 2 (STX2). The animals’ condition was indicative of HUS through three main clinical signs: thrombocytopenia, hemolytic anemia and decreased kidney function. Tissue factor antigen in the kidneys varies between animals that exhibited HUS when compared to those that had recovered or treated with anti-STX2 antibody. Overall, tissue factor is strongly detected in the renal tubules of those afflicted with HUS; tissue factor was not strongly expressed in the glomerular epithelial space, as it was in recovered, clinically healthy animals. This suggests a change throughout the time course of disease and recovery. Investigating tissue factor’s role, if any, in the pathology of the disease could lead to new therapeutics. Although many types of treatments have been suggested and tried, the primary clinical procedure is to administer fluids and allow symptoms to subside. With increasing knowledge about HUS through studies like these, we can hope to gain insight into potent therapeutics and therefore, save lives associated with typical HUS.