862 IN VITRO STUDIES OF THE PATHOGENESIS OF TRANSIENT ERYTHROBLASTOPENIA OF CHILDHOOD (TEC)

To explore the nature of the defect in TEC, we utilized the plasma clot culture technique to study the effect of patients' serum on the proliferation of erythroid stem cells in vitro. Six patients with TEC, ages 1-4 yr., presented with an average hemoglobin of 6.2gm/dl and reticulocytopenia. Bone marrow (BM) aspiration revealed decreased or absent erythroblasts. Recovery was evident by 2 weeks in all patients. When 6x104 BM mononuclear cells obtained from 4 patients at the time of diagnosis were plated with 2 I.U. of erythropoietin, 1 patient had increased numbers (159) of CFU-E-derived colonies, 2 had decreased numbers (2;18), and in 1 patient there was none (Nl:58±6). Addition of 10% patient's serum to this syngeneic system resulted in 100% inhibition of erythroid colony formation in the patient with increased numbers of CFU-E, no effect on those with decreased colonies, and increased colony formation in the patient with absent CFU-E's compared to controls. When serum from the 2 other patients was added to allogeneic BM cells in culture, there was 58 and 81% inhibition of CFU-E-derived colony formation compared to controls. Study of recovery serum from the 3 patients with inhibitors revealed loss of inhibitory activity. We conclude that while TEC has a uniform clinical presentation, there are at least two pathogenetic mechanisms:(l)a serum inhibitor directed against erythroid stem cells and (2)an abnormality of erythroid stem cells either in number or in responsiveness to erythropoietin.