• Ahn, Yeon (PI)

Project: Research project

Project Details


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.
Effective start/end date9/5/858/31/89


  • National Institutes of Health


  • Medicine(all)


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