|
|
Prepublished online as a Blood First Edition Paper on May 17, 2002; DOI 10.1182/blood-2002-01-0035.

Submitted January 8, 2002
Accepted March 20, 2002
INTRACELLULAR INTERFERON- (IFN- ) IN CIRCULATING AND MARROW T CELLS DETECTED BY FLOW CYTOMETRY AND THE RESPONSE TO IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH APLASTIC ANEMIA
Elaine M Sloand*, Sonnie Kim, Jaroslaw Maciejewski, John Tisdale, Dean Follman, and Neal S Young
Hematology Branch, National Institutes of Health, Bethesda, MD, USA
* Corresponding author; email: sloande{at}nih.gov.
Immunosuppressive therapy leads to meaningful hematologic improvement in most patients with aplastic anemia (AA). Failure to respond and later relapse could be due to deficient numbers of hematopoietic stem cells, inadequate treatment of the immune process, or a non-immunologic etiology. Interferon- (IFN- ) has been implicated in the pathophysiology of hematopoietic failure in AA. Based on previous findings showing over-expression 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 patients AA, using intracellular two color fluorescent staining and flow cytometry. Thirty-six of seventy patients (51%) with severe AA demonstrated increased IFN- in circulating T cells. IFN- was detected in only four of 53 patients with recovered 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, 27/28 (96%) with circulating IFN- -containing T cells subsequently responded to therapy; in contrast, only 11/34 (32%) of 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 re-institution of immunosuppressive drugs. Of 30 BMs tested prior to first treatment, 20 were positive for IFN- , all in responding patients, while the negative tests were obtained in ten non-responding patients. IFN- is increased in PB lymphocyte 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.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
S. O. Omokaro, M. J. Desierto, M. A. Eckhaus, F. M. Ellison, J. Chen, and N. S. Young
Lymphocytes with Aberrant Expression of Fas or Fas Ligand Attenuate Immune Bone Marrow Failure in a Mouse Model
J. Immunol.,
March 15, 2009;
182(6):
3414 - 3422.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Chen, F. M. Ellison, M. A. Eckhaus, A. L. Smith, K. Keyvanfar, R. T. Calado, and N. S. Young
Minor Antigen H60-Mediated Aplastic Anemia Is Ameliorated by Immunosuppression and the Infusion of Regulatory T Cells
J. Immunol.,
April 1, 2007;
178(7):
4159 - 4168.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. M. Sloand, L. Pfannes, G. Chen, S. Shah, E. E. Solomou, J. Barrett, and N. S. Young
CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins
Blood,
March 15, 2007;
109(6):
2399 - 2405.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. C. Bagby and G. Meyers
Bone Marrow Failure as a Risk Factor for Clonal Evolution: Prospects for Leukemia Prevention
Hematology,
January 1, 2007;
2007(1):
40 - 46.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. S. Young, R. T. Calado, and P. Scheinberg
Current concepts in the pathophysiology and treatment of aplastic anemia
Blood,
October 15, 2006;
108(8):
2509 - 2519.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. E. Solomou, K. Keyvanfar, and N. S. Young
T-bet, a Th1 transcription factor, is up-regulated in T cells from patients with aplastic anemia
Blood,
May 15, 2006;
107(10):
3983 - 3991.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Sugimori, T. Chuhjo, X. Feng, H. Yamazaki, A. Takami, M. Teramura, H. Mizoguchi, M. Omine, and S. Nakao
Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia
Blood,
February 15, 2006;
107(4):
1308 - 1314.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. S. Young
Pathophysiologic Mechanisms in Acquired Aplastic Anemia
Hematology,
January 1, 2006;
2006(1):
72 - 77.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. C. Platanias
Interferon-inducible genes and aplastic anemia
Blood,
January 1, 2006;
107(1):
2 - 3.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Zeng, A. Miyazato, G. Chen, S. Kajigaya, N. S. Young, and J. P. Maciejewski
Interferon-{gamma}-induced gene expression in CD34 cells: identification of pathologic cytokine-specific signature profiles
Blood,
January 1, 2006;
107(1):
167 - 175.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Risitano
New Challenges to Developing Animal Models for Human Immune-Mediated Marrow Failure
Clin. Med. Res.,
May 1, 2005;
3(2):
63 - 64.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Wenxin, F. Jinxiang, W. Yong, L. Wenxiang, S. Wenbiao, and Z. Xueguang
Expression of membrane-bound IL-15 by bone marrow fibroblast-like stromal cells in aplastic anemia
Int. Immunol.,
April 1, 2005;
17(4):
429 - 437.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. C. Bagby, J. M. Lipton, E. M. Sloand, and C. A. Schiffer
Marrow Failure
Hematology,
January 1, 2004;
2004(1):
318 - 336.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Zeng, G. Chen, S. Kajigaya, O. Nunez, A. Charrow, E. M. Billings, and N. S. Young
Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers
Blood,
January 1, 2004;
103(1):
325 - 332.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Hirano, M. O. Butler, M. S. von Bergwelt-Baildon, B. Maecker, J. L. Schultze, K. C. O'Connor, P. H. Schur, S. Kojima, E. C. Guinan, and L. M. Nadler
Autoantibodies frequently detected in patients with aplastic anemia
Blood,
December 15, 2003;
102(13):
4567 - 4575.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. P. Maciejewski, E. M. Sloand, O. Nunez, C. Boss, and N. S. Young
Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia
Blood,
November 15, 2003;
102(10):
3584 - 3586.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|