HUMAN MONOCLONAL ANTIBODIES

我们的目标是确定自身免疫反应的性质

Our objective is to define the nature of the autoimmune response in patients with idiopathic thrombocytopenic purpura (ITP). Specifically, we will isolate human monoclonal antiplatelet antibodies from Epstein Barr Virus transformed B lymphocytes, isolated from patients with ITP, to identify platelet autoantigens. This approach allows us t examine the spectrum of autoantibodies produced and the nature of those epitopes of GPIIb-IIIa or GPIb which serve as membrane target antigens. Our long term goal is to provide new insights into the etiology of ITP and develop safer treatment regimens for those patients with chronic ITP. Our goals in the next year include: 1.) production of anti-GPIb and anti-GPIb-IIIa specific autoantibody cell lines from a series of patients known to contain serologically defined idiotypic antiplatelet antibodies in their plasma. 2.) examination of the variable gene region of these cell lines to determine the a.)degree of polymorphism present and b.) the association of these specific somatic mutations with anti-GPIb reactivity. 3.) utilization of human monoclonal anti-GPIb-IIIa or Ib-IX antibodies to map immunogenic regions on these molecules. 4,) Continued use of these anti-idiotypic antibodies for the detection and characterization of GPIb-specific antibodies in the sera of patients with ITP and to identify those patients in whom more aggressive therapeutic regimens may be indicated.