gamma-Interferon gene expression in the bone marrow of patients with aplastic anemia.
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.


METHODS
Clinical Center, National Institutes of Health.


METHODS
25 patients with aplastic anemia on presentation, 18 patients after treatment, 39 patients with other hematologic syndromes, and 20 normal controls.


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 expression was not a simple function of the number of lymphocytes in samples.


CONCLUSIONS
gamma-Interferon expression is prevalent in acquired aplastic anemia and may be a specific marker of this disease. Local production of this inhibitory lymphokine in the target organ, the bone marrow, may be important in mediating aplastic anemia. Measurement of this lymphokine's message may be useful in distinguishing acquired aplastic anemia from other forms of bone marrow failure.
Nisticò
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A
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Young
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NS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism*; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000097:blood
D012333:RNA, Messenger; D007371:Interferon-gamma