Gamma-Interferon Gene Expression in the Bone Marrow of Patients with Aplastic Anemia

Abstract

Objective To determine gamma-interferon gene expression in the bone marrow of patients with aplastic anemia and controls. Most patients with acquired aplastic anemia respond to immunosuppressive therapy, implicating an immune pathophysiologic origin for this disease. Setting Clinical Center, National Institutes of Health. Patients 25 patients with aplastic anemia on presentation, 18 patients after treatment, 39 patients with other hematologic syndromes, and 20 normal controls. Measurements and main results gamma-Interferon signal was detected in the bone marrow of 14 of 18 patients with severe aplasia on presentation, 4 of 7 patients with moderate aplastic anemia, and 1 of 2 patients with the paroxysmal nocturnal hemoglobinuria-aplasia syndrome. The gamma-interferon gene was not expressed in marrow from 20 normal persons or in patients who had received many transfusions for chronic anemia; with pancytopenia after chemotherapy; or with marrow failure of other types, including myelodysplasia, inherited anemias, or constitutional aplastic anemia. In serial studies, gamma-interferon RNA disappeared from the marrow of patients as they responded to immunosuppression; the signal was present in 3 of 4 patients who had a relapse but not in previously treated, now recovered patients. Determination of marrow gamma-interferon gene expression was more specific and sensitive than concurrent determinations in peripheral blood. Quantitative titration of mRNA showed that gamma-interferon expr…