PATHOGENESIS OF THE IMMUNE THROMBOCYTOPENIAS

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Immune thrombocytopenic purpura (ITP) results from immunologic injury to the platelet by either antiplatelet antibody or immune complexes with resulting platelet destruction. The condition may be primary (idiopathic) or secondary to drugs, isoantibodies or associated with other diseases (e.g. SLE). Previous studies from our laboratory have focused on antiplatelet antibody (synthesis, target tissues and quantification). In the present proposal we will extend our studies into the following three areas where experimental information is sparse: (1) Platelet antigens, (2) Complement fixation and platelet phagocytosis, (3) Immunoregulation. Platelet antigens will be studied by reacting radiolabeled antiplatelet antibody from patient sera or from cultures of their splenic cells with solubilized platelet proteins immobilized on nitrocellulose paper after transfer from polyacrylamide slab gels. If identified, the antigens will be purified and characterized. The role of the classical alternative complement pathways in ITP will be comprehensibly evaluated using in vitro tests to determine serum levels of activated C4 and factor B as well as platelet and megakaryocyte bound C3, factor B and C5-9 attack complexes. In selected patients, the in vivo metabolism of complement proteins will be studied and correlated with the patients' platelet survival. Platelet phagocytosis will be studied by incubating radiolabeled platelets with purified antiplatelet antibody and complement components and observing the effect of these maneuvers on their ingestion by leukocytes. In addition, T and B lymphocyte function will be evaluated using in vitro culture methods to further document the presence of a T suppressor defect and determine if it is primary or secondary. Our studies will be correlated with the patients' clinical status.