DANAZOL IN IMMUNE THROMBOCYTOPENIA AND HEMOLYTIC ANEMIA

  • Ahn, Yeon, (PI)

Project: Research project

Description

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

Funding

  • National Institutes of Health

Fingerprint

Danazol
Idiopathic Thrombocytopenic Purpura
Hemolytic Anemia
Autoimmune Hemolytic Anemia
T-Lymphocyte Subsets
Lymphocytes
Glucocorticoids
Therapeutics
Complement C2
Complement 3b Receptors
Fc Receptors
Complement Activation
Gonadal Steroid Hormones
Splenectomy
Lymphocyte Activation
Serum
Autoimmunity
Androgens
Autoimmune Diseases
Antibody Formation

ASJC

  • Medicine(all)