AN IDIOTYPIC NATURAL AUTOANTIBODY NETWORK IN HEMOLYTIC UREMIC SYNDROME (HUS).† 1020

Introduction: We hypothesized that immune-mediated events rather than direct toxin injury might be involved in the pathogenesis of HUS associated with shiga-like toxin (SLT) producing E. coli. Purposes: Our objectives were to learn whether antibodies (AB) exist to the SLT glycolipid receptor Gb₃, to define the occurrence and relationship between such anti-Gb₃ ABs (α-Gb₃) and anti-idiotypic ABs to them (α-α-Gb₃), and to evaluate children infected with E. coli O157:H7 for these ABs.Methods: ELISAs were used for detecting α-Gb₃ orα-α-Gb₃ in sera from normal adults [n=15] and from children with E. coli O157:H7 associated with [n=24] or without [n=38] development of HUS. Results: Normals have both α-Gb₃ and α-α-Gb₃; levels of these ABs are correlated [r=0.9654]. The relationship between these antibodies in E. coli O157:H7 infection is shown below: Table Conclusions:(1) Autoantibodies to Gb₃ are normally found. (2) α-Gb₃ exists in balance with α-α-Gb₃. (3) Children with HUS during the acute phase have significantly decreased levels of these ABs. We hypothesize that these ABs are low because α-α-Gb₃ binds to SLT leaving α-Gb₃ available to bind to Gb₃ of endothelial cells and induce vascular injury. [Supported in part by NIH-PO1 HD-13021]

Table 1