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-mediated glomerulonephritis and thrombocytopenia. Although the presence of cross-reactive anti-phospholipid antibodies in sera of MRL/lpr mice has been demonstrated, possible relationships between detected autoantibodies and the development of thrombocytopenia have not been elucidated. Recent genetic analyses 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 autoantibody-producing hybridoma cells from MRL/lpr mice, we identified an IgG2a-producing anti-gp70 hybridoma clone that induced microvascular intraluminal platelet aggregation, thrombocytopenia, and amenia upon transplantation into syngeneic non-autoimmune mice. This and two other anti-gp70 antibodies bound 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 pathogenic anti-gp70 autoantibody specifically precipitated a platelet protein with an approximate relative molecular mass of 40 000.
Hashimoto
K
K
Department of Immunology, Third Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
Tabata
N
N
Fujisawa
R
R
Matsumura
H
H
Miyazawa
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001323:Autoantibodies / Q000008:administration & dosage*; D001792:Blood Platelets / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006825:Hybridomas / Q000276:immunology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D010974:Platelet Aggregation / Q000276:immunology; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D014759:Viral Envelope Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins