PATHOGENESIS OF THE IMMUNE THROMBOCYTOPENIAS

免疫性血小板减少性紫癜(ITP)是由机体免疫损伤引起的 通过抗血小板抗体或免疫复合物产生的血小板 破坏了血小板。这种情况可能是原发的(特发性)，也可能是继发性的 药物、同种抗体或与其他疾病(如系统性红斑狼疮)有关。上一首 我们实验室的研究主要集中在抗血小板抗体(合成， 靶组织和量化)。在本提案中，我们将延长我们的 对实验信息稀缺的以下三个领域进行研究： (1)血小板抗原，(2)补体结合和血小板吞噬，(3) 免疫调节。 将通过反应放射性标记的抗血小板抗体来研究血小板抗原 从患者血清或从他们的脾细胞培养物中溶解 硝酸纤维素纸转移后固定化的血小板蛋白 聚丙烯酰胺平板凝胶。如果被确认，抗原将被提纯并 特色化的。经典替代补体途径在ITP中的作用 将使用体外测试来确定血清水平，以进行全面评估 活化的C4和B因子以及与血小板和巨核细胞结合的C3， B因子和C5-9攻击复合体。在选定的患者中，体内的 补体蛋白的新陈代谢将被研究并与 患者的血小板存活率。将通过以下方法研究血小板吞噬功能 纯化的抗血小板抗体与放射性标记的血小板孵育 补充成分并观察这些动作对其功能的影响 被白细胞摄取。此外，T和B淋巴细胞的功能将 使用体外培养方法进行评估以进一步证明T细胞的存在 抑制缺陷并确定它是主要缺陷还是次要缺陷。我们的研究将 与患者的临床状态相关。

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.