title: Haemolytic uraemic syndrome is an immune-mediated disease: role of anti-CD36 antibodies.
abstract: Haemolytic uraemic syndrome (HUS) is a disorder in which platelet microthrombi are formed that have a particular propensity to deposit in the kidney microvasculature, resulting in impaired renal function and thrombocytopenia. The mechanism of formation of these microthrombi is not known. In this study, we showed that plasma from five adult and six paediatric cases of HUS caused aggregation and release of adenosine triphosphate from normal platelets. The plasma reacted against platelet lysate in a protein blot and all samples showed reactivity against a band at 88 kDa, corresponding to the membrane antigen CD36. This was confirmed by probing with Mo91, a monoclonal antibody to CD36. CD36 was also identified in the immune complex formed by incubation of patient plasmas with normal platelet lysate. In other studies, bands of 32 and 7.7 kDa were obtained when purified verotoxin was protein blotted and probed with either patient plasma or with anti-CD36 antibody Mo91 suggesting structural homologies between CD36 and verotoxin. While a direct cause-effect relationship is not yet established, the data support the concept of an immunological pathogenesis for HUS and suggest that molecular mimicry involving one or both of the homologous domains in membrane-bound CD36 and verotoxin lead to the development of antibodies capable of inducing the pathophysiological events characteristic of HUS.
authors.affiliation: Division of Hematology and Transfusion Medicine, Department of Pathology and Laboratory Medicine, Ottawa Hospital, Ottawa, ON, Canada. grock@ottawahospital.on.ca
authors.forename: Gail
authors.initials: G
authors.lastname: Rock
authors.forename: William
authors.initials: W
authors.lastname: Clark
authors.forename: Marion
authors.initials: M
authors.lastname: Sternbach
authors.forename: Maria
authors.initials: M
authors.lastname: Kolajova
authors.forename: Peter
authors.initials: P
authors.lastname: McLaine
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000071120:ADAMTS13 Protein; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000378:metabolism / Q000502:physiology*; D018955:CD36 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008833:Microcirculation; D018716:Molecular Mimicry; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D022603:Shiga Toxins / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D018955:CD36 Antigens; D022603:Shiga Toxins; D014841:von Willebrand Factor; D000255:Adenosine Triphosphate; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human