Experimental Strategies for Diagnosis, Prevention and Treatment of Hemolytic Uremic Syndrome.

GOMEZ FERNANDO; LUZ DANIELA; PORPORATO MELINA; GIRÓN DANIEL; BALESTRACCI ALEJANDRO; ALCONCHER LAURA; IBARRA CRISTINA; PIAZZA ROXANE MP; SACERDOTI FLAVIA; AMARAL MARÍA MARTA

Mar del Plata

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2023

SAIC

Shiga toxin-producing E. coli (STEC) is responsible for dfferent clinical conditions including a serious systemic disease known as hemolytic uremic syndrome (HUS). HUS is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury (AKI). Argentina has the highest incidence worldwide with 8–12 ases/100000 per year. Shiga toxin (Stx) is the main virulence factor of STEC that circulates in the bloodstream found to different cells or within blood-cell-derived microvesicles (MVs). Stx binds to the globotriaosylceramide (Gb3) receptor on the cell membrane of target ells and develops apoptosis. Stx cytotoxic effects, and he clinical features that follow, are a result of damage in the endothelial cells of small vessels mainly localized in the colon, kidney, and central nervous system. Shiga toxin type 2 (Stx2) seriously affects the kidney because of the presence of especially Stx sensitive cells that express considerable amounts of Gb3 receptors. The early diagnosis of STEC infection is important to avoid chronic sequelae and long internment periods. MVs containing Stx (MVs-Stx) were reported to contribute to HUS physiopathology and disease. In this sense, we developed he detection of circulating MVs-Stx2 in a rat model of HUS, proposing them as a new biomarker that may help he early diagnosis. We were able to detect, by flow cytometry, circulating MVs-Stx2 in blood samples, 96 h after Stx2 injection. Following, we analyzed circulating MVs-Stx2 in HUS patients. From the controls, a cut-off point for MVs-Stx2 was established (1.02-1.90 %, n =5). We found a significantly higher percentage of MVs-Stx2 in HUS patients with respect to healthy controls (P1: 3.63%, P2: 5.20%, p