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Prepublished online as a Blood First Edition Paper on May 17, 2002; DOI 10.1182/blood-2002-01-0035.
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Blood, 15 August 2002, Vol. 100, No. 4, pp. 1185-1191
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Intracellular interferon- in circulating and marrow T cells
detected by flow cytometry and the response to immunosuppressive
therapy in patients with aplastic anemia
Elaine Sloand,
Sonnie Kim,
Jaroslaw P. Maciejewski,
John Tisdale,
Dean Follmann, and
Neal S. Young
From the Hematology Branch, National Heart, Lung, and
Blood Institute, National Institutes of Health, Bethesda, MD.
Immunosuppressive therapy leads to meaningful hematologic
improvement in most patients with aplastic anemia (AA). Failure to
respond and a later relapse could be due to deficient numbers of
hematopoietic stem cells, inadequate treatment of the immune process,
or a nonimmunologic etiology. Interferon- (IFN- ) has been
implicated in the pathophysiology of hematopoietic failure in AA. On
the basis of previous findings showing overexpression of IFN- in
bone marrow (BM) and peripheral blood (PB) in this disease, we
hypothesized that quantitation of IFN- might be applied to predict
and monitor responses to immunosuppressive therapy. We measured
expression of IFN- in lymphocytes obtained from 123 AA patients,
using intracellular 2-color fluorescent staining and flow cytometry. Of
70 patients with severe AA, 36 (51%) demonstrated increased
IFN- in circulating T cells. IFN- was detected in only 4 of 53 patients who had recovered from AA. IFN- was not found in PB
lymphocytes of patients with other hematologic diseases and heavy
transfusion burdens or in healthy volunteers. Among 62 AA patients who
were assessed before first treatment with immunosuppressive drugs, 27 of 28 (96%) with circulating IFN- -containing T cells subsequently
responded to therapy; in contrast, only 11 of 34 (32%) patients whose
PB lacked IFN- lymphocytes improved to transfusion independence.
IFN- -containing lymphocytes declined following treatment in all
cases. Of 17 patients assessed during relapse, IFN- was present in T
cells prior to the blood count decline in 13, and 12 responded to
reinstitution of immunosuppressive drugs. Of 30 BMs tested prior to
first treatment, 20, all in responding patients, were positive for
IFN- , whereas the negative tests were obtained in 10 nonresponding
patients. IFN- is increased in the PB lymphocytes of many
patients with AA, and these cells decline with therapy. The presence of
intracellular IFN- may predict response to immunosuppressive
treatment and also the onset of relapse.

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