Induction of microthrombotic thrombocytopenia in normal mice by transferring a platelet-reactive, monoclonal anti-gp70 autoantibody established from MRL/lpr mice: an autoimmune model of thrombotic thrombocytopenic purpura

MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop immune complex-mediate d glomerulonephritis and thrombocytopenia. Although the presence of cross-r eactive anti-phospholipid antibodies in sera of MRL/lpr mice has been demon strated, possible relationships between detected autoantibodies and the dev elopment of thrombocytopenia have not been elucidated. Recent genetic analy ses in a few different strains of lupus-prone mice have pointed out a close correlation between autoantibodies reactive with endogenous retroviral env gene product, gp70, and the development and severity of glomerulonephritis . In the process of establishing possibly nephritogenic anti-gp70 autoantib ody-producing hybridoma cells from MRL/lpr mice, we identified an IgG2a-pro ducing anti-gp70 hybridoma clone that induced microvascular intraluminal pl atelet aggregation, thrombocytopenia, and amenia upon transplantation into syngeneic non-autoimmune mice. This and two other anti-gp70 antibodies boun d onto the surface of mouse platelets, and purified IgG2a of the anti-gp70 autoantibody induced glomerular lesions with characteristics of thrombotic thrombocytopenic purpura when injected into non-autoimmune mice. The pathog enic anti-gp70 autoantibody specifically precipitated a platelet protein wi th an approximate relative molecular mass of 40 000.