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Prepublished online as a Blood First Edition Paper on March 27, 2003; DOI 10.1182/blood-2002-09-2748.
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Blood, 15 July 2003, Vol. 102, No. 2, pp. 763-771
TRANSPLANTATION
Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays
Tamotsu Ichiba,
Takanori Teshima,
Rork Kuick,
David E. Misek,
Chen Liu,
Yuichiro Takada,
Yoshinobu Maeda,
Pavan Reddy,
Debra L. Williams,
Samir M. Hanash, and
James L. M. Ferrara
From the Departments of Internal Medicine and Pediatrics, University of Michigan Cancer Center, Ann Arbor; the Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville; and the Department of Ophthalmology, University of Michigan Kellogg Eye Center, Ann Arbor
The liver, skin, and gastrointestinal tract are major target organs of acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT). In order to gain a better understanding of acute GVHD in the liver, we compared the gene expression profiles of livers after experimental allogeneic and syngeneic BMT using oligonucleotide microarray. At 35 days after allogeneic BMT when hepatic GVHD was histologically evident, genes related to cellular effectors and acute-phase proteins were up-regulated, whereas genes largely related to metabolism and endocrine function were down-regulated. At day 7 after BMT before the development of histologic changes in the liver, interferon  (IFN-)–inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN- protein itself was increased in the spleen but not in hepatic tissue. These results suggest that the increased expression of genes associated with the attraction and activation of donor T cells induced by IFN- early after BMT is important in the initiation of hepatic GVHD in this model and provide new potential molecular targets for early detection and intervention of acute GVHD.
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