Mechanism of microthrombosis in HUS

• Published in: Kidney international Vol. 75; no. 112s; pp. S15 - S16
• Main Authors: Rock, Gail A, Clark, William F
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2009; Elsevier Limited
• Subjects: Adenosine Triphosphate - blood; Adult; anti-CD36 antibodies; Antibody Specificity; Autoantibodies - blood; Blood Platelets - immunology; Blood Platelets - metabolism; CD36 Antigens - immunology; Child; Cross Reactions; hemolytic uremic syndrome; Hemolytic-Uremic Syndrome - blood; Hemolytic-Uremic Syndrome - immunology; Humans; microthrombosis; Microvessels - immunology; Molecular Mimicry; Platelet Aggregation; Shiga Toxin 2 - immunology; Thrombosis - blood; Thrombosis - immunology; verotoxin; molecular mimicry; anti-CD36 antibodies; microthrombosis; hemolytic uremic syndrome; verotoxin
• ISSN: 0085-2538; 0098-6577; 1523-1755
• DOI: 10.1038/ki.2008.611

The mechanism of formation of the microthrombi in hemolytic uremic syndrome (HUS) is not known. Plasma from five adult and six pediatric cases of HUS showed aggregation and release of adenosine triphosphate from normal platelets. When the plasma was absorbed with staphylococcal protein A and again exposed to normal platelets there was no aggregation or release, indicating that an antibody was responsible for the aggregation. The plasma reacted with platelet lysate in a western blot, showing reactivity with CD36. This was confirmed by probing with Mo91, a monoclonal antibody to CD36. When the patient's plasma was used to probe purified verotoxin-2, bands of 32 and 7.7 kDa were obtained. Similar results were obtained using Mo91. The reactions suggest structural homologies between CD36 and verotoxin. Although a direct cause–effect relationship is not yet established, the data support the concept of an immunological pathogenesis for HUS with the formation of cross-reacting antibodies.