Anti-CD36 antibodies in thrombotic thrombocytopenic purpura

Abstract

The membrane glycoprotein CD36 (GPIV, M(r) 88,000) is found on platelets, monocytes and endothelial cells of the microvasculature. In the present study, anti CD36 antibodies have been identified as occurring with high frequency in patients with thrombotic thrombocytopenic purpura. The presence of anti CD36 antibodies in 15 TTP plasma samples thought to contain them on the basis of an initial screening by protein blots was confirmed by re-screening against a standard of purified CD36, by immunoprecipitation from 125I-labelled control platelets and by dot blots against purified CD36. In a further 28 random samples examined, 23/27 (85%) were CD36-positive by immunoprecipitation, 21/28 (75%) by protein blotting, and 17/28 (60%) by dot blots against purified CD36. On protein blots following SDS-PAGE, immunoprecipitates produced from normal platelets by TTP plasma gave positive reactions with the anti CD36 monoclonal antibody 125I-Mo91. One half of the total TTP samples examined (21/42) caused approximately 70% release in control platelets loaded with 14C-serotonin. Of samples causing release > or = 70%, one-half (8/15) failed to cause release from Naka-negative platelets which constitutively lack CD36 showing that CD36 was the sole target for platelet activation in these TTP samples. These studies demonstrate that antibodies directed against CD36 occur frequently in TTP patients and could cause thrombotic complications and vascular damage by reacting with the parent antigen present in platelets and endothelial cells.