PATHOGENESIS AND IMMUNOLOGY OF INFECTIOUS PROCESSES
Our laboratory has been working for several years on the pathogenesis of Hemolytic Uremic Syndrome (HUS), and the development of treatments and vaccines, since up to date there is none is of these. HUS is an endemic disease In Argentina, with the highest annual incidence in the world: 10-12 / 100,000 children under 5 years of age. Enterohemorrhagic Escherichia coli (EHEC) O157: H7 is the main etiologic agent, and Shiga toxin (Stx) is absolutely necessary for progression to HUS. Given that 10-15% of patients infected with EHEC evolve to HUS, our hypothesis has been that in addition to the bacteria's own factors (virulence factors, infective dose, etc.), the host factors during pathogen-immune response interaction defines the outcome of the infection to self-contained or to severe, systemic forms. It is estimated that 35-40% of HUS patients will have renal or neurological sequelae, of different degrees, for life.
Thus, we have focused on the study of the systemic inflammatory and anti-inflammatory response, and the local response in the intestinal mucosa. In both cases we analyze the innate and the specific (or adaptive) immune responses.
Based on the hypothesis that the protective capacity of specific antibodies could avoid HUS outcome, we have engineered a highly effective immunogen at developing specific antibodies against the Stx toxin and generating protection in the host. This product has been patented and is the basis for the development of a treatment for HUS based on equine antibodies currently (Phase III)
In parallel, we have analyzed bacterial biology and the regulation of virulence factors during the interaction with the intestinal microbiome.
We have developed different murine models of HUS, based on Stx intoxication and EHEC infection, which are extremely useful in modeling the human disease. We also study pediatric patients with HUS during the acute phase or after a recovery period.
Chair: Marina S Palermo, PhD. CONICET Senior researcher.
E-mail: marinasandrapalermo@gmail.com