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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
7R01DK033345-09
Application #
3231758
Study Section
Experimental Immunology Study Section (EI)
Project Start
1984-01-01
Project End
1995-01-31
Budget Start
1993-07-01
Budget End
1994-01-31
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Children's Hospital of Orange County
Department
Type
DUNS #
City
Orange
State
CA
Country
United States
Zip Code
92868
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