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A cell culture system1' 2 in which human bone marrow responds to the in vitro addition of erythropoietin with increased heme synthesis provides a new means of studying disorders of red cell production, and has already been used to study the erythropoietic response of marrow from patients with polycythemia vera.3 This method should also prove useful in the investigation of those diseases of underproduction of red cells where enough marrow can be obtained to perform the study. Such a disease is pure red cell aplasia in which the marrow has a normal cellularity with only a deficient number of red cell precursors. Several investigators4-7 have suggested that this disease is due to an autoimmune state, but little evidence of a circulating inhibitor to erythropoiesis has so far been presented. Our studies of a patient with red cell aplasia show that his marrow not only responds to added erythropoietin in vitro with an increased rate of heme synthesis, but also develops an enhanced control level of heme synthesis when separated from high concentrations of his plasma. In addlition, the patient's plasma inhibits heme synthesis of normal marrow in vitro, and contains an antibody to erythroblast nuclei. These findinlgs, taken with the patient's recovery to a normal state after treatment with 6-mercaptopurine, an immunosuppressive agent, all lend support to the idea that this disease may be due to a circulating antibody.

Studies on red cell aplasia. I. Demonstration of a plasma inhibitor to heme synthesis and an antibody to erythroblast nuclei.