Minimal evidence of platelet and endothelial cell reactive antibodies in thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by mi crovascular thrombosis with thrombocytopenia and end-organ injury. Evidence suggests that platelet or endothelial cell injury may be initial pathologi cal events in TTP. A number of factors in patient plasma, including immunog lobulins, have been proposed to mediate cellular injury In TTP. However, sy stematic analyses of TTP patient plasma for the presence of platelet or end othelial cell antibodies are lacking. We, therefore, analyzed 48 TTP patien t plasma samples for the presence of platelet and endothelial cell antibodi es by using enzyme-linked Immunosorbent assay, flow cytometry, and microlym phocytotoxicity, Twelve of 48 TTP patient samples (25%) reacted against pur ified platelet glycoproteins. Nine (19%) also contained antibodies that bou nd to allogeneic target platelets in flow-cytometric assays. Nine of 48 sam ples (19%) contained antibodies to human umbilical vein endothelial cells i n flow-cytometric assays, and seven of 48 patient samples (15%) bound to hu man dermal microvascular endothelial cells. Six of 48 (13%) patient plasma samples contained antibodies that bound to human umbilical vein endothelial cells activated with gamma-interferon and tumor necrosis factor-alpha. Of twenty samples that were reactive in one or more platelet or endothelial ce ll assay, eight contained human leukocyte antigen antibodies reactive in mi crolymphocytotoxicity. These studies demonstrate that antibodies reactive a gainst platelet or endothelial cell antigens are not prevalent in TTP, and that more than a third of antibodies detected are human leukocyte antigen a lloantibodies. Our findings suggest that autoantibodies against platelets o r endothelial cells are not important in the pathogenesis of this syndrome. Am. J. Hematol. 62:82-87, 1999. (C) 1999 Wiley-Liss, Inc.