PATHOGENESIS OF THE IMMUNE THROMBOCYTOPENIAS

免疫性血小板减少性紫癜（ITP）是由于免疫系统的免疫损伤， 血小板通过抗血小板抗体或免疫复合物， 血小板破坏 这种情况可能是原发性（特发性）或继发于 药物、同种抗体或与其他疾病（如SLE）相关。 先前 我们实验室的研究集中在抗血小板抗体（合成， 靶组织和定量）。 在本提案中，我们将扩大我们的 在以下三个实验信息稀少的领域开展研究： (1)血小板抗原，（2）补体结合和血小板吞噬作用，（3） 免疫调节。 将通过放射性标记的抗血小板抗体反应研究血小板抗原 从患者血清或从其脾细胞的培养物中 转移后固定在硝酸纤维素纸上的血小板蛋白 聚丙烯酰胺平板凝胶。 如果鉴定出抗原，则将抗原纯化并 表征了 经典补体旁路途径在ITP中的作用 将使用体外试验进行全面评价，以确定血清水平 活化的C4和因子B以及血小板和巨核细胞结合的C3， 因子B和C5-9攻击复合物。 在选定的患者中， 将研究补体蛋白质的代谢，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作用： 用纯化的抗血小板抗体孵育放射性标记的血小板， 补充成分，并观察这些演习对他们的影响， 被白细胞摄取 此外，T和B淋巴细胞功能将 使用体外培养方法进行评价，以进一步证明T细胞的存在。 抑制基因缺陷，并确定它是主要的还是次要的。 我们的研究将 与患者的临床状况相关。

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.