Testosterone reduces complement sensitivity of precursor cells in aplastic anaemia patients treated with antilymphocyte globulin

Abstract

Of 53 consecutive patients with aplastic anaemia who were re-examined at various intervals after treatment with antilymphocyte globulin, 30 had sufficient bone marrow colony forming capacity to permit evaluation of androgen effects in vitro. In 22 patients, precursor cells of the myeloid and erythroid line were abnormally sensitive to a preincubation in isosmolar sucrose with 5% fresh autologous serum compared to heat-inactivated autologous serum. This phenomenon was interpreted as excess complement sensitivity. This inhibitory effect of fresh serum in the bone marrow sucrose test was abrogated by addition of 10(-6) M testosterone to the preincubation phase in 15 of the 22 patients. In six of these 15, 10(-7) M dexamethasone had a similar effect; in the other nine patients only testosterone rendered the bone marrow sucrose test negative. This effect of testosterone on colony growth was indirect, since addition of 10(-9)-10(-5) M testosterone to primary bone marrow cultures from the same patients had no effect. We propose that testosterone in these experiments interacted with the complement system. In patients who have complement sensitive precursor cells, androgens might thus prevent complement mediated lysis of haemopoietic cells to some extent. The test described could help identification of patients in autologous bone marrow remission who are likely to benefit from androgen treatment.