Susceptibility to Hemolytic-Uremic Syndrome Relates to Erythrocyte Glycosphingolipid Patterns

Abstract

Hemolytic-uremic syndrome (HUS) is usually preceded by enteric infection by Shiga-like toxin-producing Escherichia coli (SLT-EC), but most children with SLT-EC diarrhea do not develop HUS. SLT toxicity depends on entry into the target cell via its host cell glycolipid receptor, globotriaosylceramide (Gb₃). The relationship between differential susceptibility to HUS and erythrocyte Gb₃ levels, as measured by high-pressure liquid chromatography, was studied. Erythrocytes of children with histories of HUS had lower nonhydroxylated fatty acyl (NFA) Gb₃ levels than did erythrocytes of controls (1.6 vs. 2.0 nmolfmL of packed cells); these erythrocytes had lower ratios of NFA-Gb3 to lactosylceramide (0.16) than did erythrocytes of SLT-EC diarrheal patients without subsequent HUS (0.30; P < .003) or of healthy controls (0.28; P < .001). The lower erythrocyte Gb3 levels associated with HUS may reflect a genetic predisposition for differential outcomes of SLT-EC gastroenteritis.