DANAZOL IN IMMUNE THROMBOCYTOPENIA AND HEMOLYTIC ANEMIA

达那唑治疗免疫性血小板减少症和溶血性贫血

• 批准号: 3232211
• 负责人: Yeon S. Ahn
• 金额: $ 13.22万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-05 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232211
• 关键词: androgens; complement inhibitors; complement pathway; glucocorticoids; hemolytic anemia; human subject; human therapy evaluation; immunofluorescence technique; immunohematology; immunologic techniques; leukocyte activation /transformation; membrane activity; monoclonal antibody; monocyte; phagocytes; prednisone; radiotracer; remission /regression; splenectomy; suppressor T lymphocyte; thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are ideal models to study the efficacy and mechanism of immunosuppressive therapy in autoimmune diseases. We have reported the value of danazol, an attenuated androgen, in ITP and more recently its benefit in AIHA. Our long-range objectives are to delineate the mechanism(s) of action of danazol and thereby develop an effective and safe treatment for ITP and AIHA, based on the use of sex hormones. Hormonal manipulation of autoimmunity in humans has not been studied in depth. Therefore the knowledge gained from this study can be applicable to other autoimmune diseases of man. Specific aims are (1) to estimate response rates and side effects of danazol compared to glucocorticoids, (2) to assess its value as an alternative to long-term glucocorticoid therapy and splenectomy, and (3) to study its mechanism of action based on the hypothesis that danazol induces remission by either restoring the imbalance in T cell subsets or by inhibiting complement activation. The prospective randomized protocol of ITP is designed to achieve these goals. Patients will be randomized initially to either danazol or prednisone therapy. If they fail in one, they will receive the other in the next phase and both if neither of them induces remission. Specimens before and during danazol therapy will be collected from patients to monitor antibody levels, T cell subsets, lymphocyte functions and complement components. Data will be analyzed to determine whether danazol inhibits antibody production, MPS function, T cell function or the complement system. Such immune alterations will be correlated with clinical responses. Laboratory investigations will examine the action of danazol on the immune system focusing on three major areas: the effects of danazol on (1) lymphocyte function -a) in vitro action of danazol on normal lymphocyte function (blastogenesis, suppressor cell activity-spontaneous and inducible)-b) in vivo effects on patient's lymphocytes collected before and during therapy; (2) complement system-a) in vitro effects on the complement system in normal sera b) in vivo effects on sera drawn from patients before and during danazol therapy; and (3) modulation of Fc and C3b receptors of monocyte.

特发性血小板减少性紫癜与自身免疫性溶血性贫血 (Aiha)是研究其药效和作用机制的理想模型。 自身免疫性疾病的免疫抑制治疗。我们已经报道了 达那唑是一种减毒雄激素，在ITP及其最近的治疗中的价值 在AIHA中受益。我们的长远目标是勾勒出 达那唑的作用机理(S)，从而开发出一种有效而安全的 对ITP和AIHA的治疗，基于性激素的使用。荷尔蒙 对人类自身免疫的操纵还没有深入的研究。 因此，本研究所获得的知识可以应用于其他领域 人类的自身免疫性疾病。 具体目标是(1)估计应答率和副作用 丹那唑与糖皮质激素的比较，(2)评估其作为一种 长期糖皮质激素治疗和脾切除术的替代方案，以及(3) 根据达那唑诱导的假说研究其作用机制 通过恢复T细胞亚群的失衡或通过 抑制补体激活。 ITP的前瞻性随机化方案旨在实现这些 目标。患者最初将随机服用达那唑或 强的松疗法。如果其中一个不及格，他们将接受另一个 下一个阶段和两个阶段都不会导致缓解。标本 达那唑治疗前和治疗期间将从患者身上收集 监测抗体水平、T细胞亚群、淋巴细胞功能和 补充成分。将对数据进行分析以确定达那唑是否 抑制抗体产生、MPS功能、T细胞功能或 补充制。这种免疫变化将与 临床反应。 实验室调查将检查达那唑对免疫系统的作用 系统集中在三个主要领域：达那唑对(1)的影响 淋巴细胞功能-a)达那唑对正常淋巴细胞的体外作用 功能(原始细胞生成、抑制细胞活动-自发性和 可诱导的)-b)在体内对患者采集的淋巴细胞的影响 治疗过程中；(2)补体系统-a)体外对补体的影响 正常血清中的系统b)体内对以前患者血清的影响 在达那唑治疗期间；(3)Fc和C3b受体的调节 单核细胞。