IDENTIFICATION OF ANTIPLATELET ANTIBODY IDIOTYPlSS ASSOCIATED WITH GLYCOPROTEIN Ib SPECIFICITY, PRESENT IN ITP PLASMA AND PRODUCED BY HUMAN HYBRIDOMAS FROM ITP SPLEEN CELL FUSIONS

Platelet membrane glycoproteins (GP) express anumber of antigenic determinants important in theetiology of autoimmune thrombocytopenia. Sensitization to GPIb, although not the most frequent cause of ITP, leads to a particularly severe form ofthe disease. We have identified a number of casesof ITP in which GPIb bears the relevant immunogen. Using GPIb-specific autoantibodies isolated from the plasma of one such patient, we have produced a number of rabbit polyclonal and murine monoclonal anti-idiotypic antibodies. These antibodies recognize an idiotype expressed on the IgM antibody of this patient as well as IgG or IgM antibodies from several other patients with ITP, all of which can be shown to bind specifically to GPIb. Statistical analysis of a series of plasmas from normal individuals and thrombocytopenic patients demonstrated that there is a very strong correlation between the presence of the idiotype and GPIb reactivity, (p < 0.00001). These anti-idiotypic antibodies are useful for the detection and characterization of GPIb-specific antibodies in the sera of patients with a clinically severe form of ITP. The classification of patients bearing this idiotype in their plasma may be useful in predicting disease outcome, thus identifying a group of ITP patients in whom more aggressive therapeutic regimens may be indicated. The use of these reagents and the development of human B lymphoblastoid cell lines producing monoclonal anti-GPIb antibodies will serve to elucidate the clonal origin and cellular regulation of autoantibody production in this disease