Our objective is to define the nature of the autoimmune response in patients with chronic idiopathic thrombocytopenic purpura (ITP). During the past year we have isolated a series of hybrid cell lines that produce human autoantibodies against platelet antigens. These hybrids were prepared by fusing EBV transformed lymphocytes from patients with ITP with a 6TG resistant NS-1 mouse myeloma-human B lymphocyte heterohybrid cell line, F6. Monoclonal antibody secreted by two of the hybrid cell lines have been identified to react with a platelet protein or glycoprotein with a molecular weight of approximately 100,000 daltons, and an antibody secreted by another line reacts with a determinant shared by a series of platelet associated proteins or glycoproteins. Specifically, we now wish to 1) prepare a library of somatic cell hybrids which secrete human antiplatelet autoantibody; and examine 2) the serological and biochemical specificity, as well as 3) the isotypic and idiotypic characteristics of the monoclonal antiplatelet autoantibodies. We will then use these reagents to 4) determine the relationship between the isotype, idiotype, and molecular specificity of serum antiplatelet antibodies and disease outcome. Our long-range goal is to use this information to develop immunologic methods for the treatments of chronic ITP.
|Gruel, Y J; Nugent, D J; Kunicki, T J (1995) Molecular specificity of anti-IIb/IIIa human antibodies. Semin Thromb Hemost 21:60-7|
|Ishida, F; Gruel, Y; Brojer, E et al. (1995) Repertoire cloning of a human IgG inhibitor of alpha IIB beta 3 function. The OG idiotype. Mol Immunol 32:613-22|
|Kunicki, T J; Annis, D S; Gorski, J et al. (1991) Nucleotide sequence of the human autoantibody 2E7 specific for the platelet integrin IIb heavy chain. J Autoimmun 4:433-46|
|Kunicki, T J; Plow, E F; Kekomaki, R et al. (1991) Human monoclonal autoantibody 2E7 is specific for a peptide sequence of platelet glycoprotein IIb. Localization of the epitope to IIb231-238 with an immunodominant Trp235. J Autoimmun 4:415-31|