Journal
CLINICAL IMMUNOLOGY
Volume 148, Issue 1, Pages 124-135Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2013.04.013
Keywords
Graft-versus-host-disease; Bone marrow transplantation; Genomic markers; Gene expression
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Funding
- NIH [R01 A1085024, P01 CA049605, P01 HL075462]
- Stanford Cancer Center [1P030CAl24435-01]
- American Society of Hematology Scholar
- Leukemia and Lymphoma Society Fellow
- Department of Defense Post-doctoral Fellow
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Chronic graft-versus-host disease (GVHD) results in significant morbidity and mortality, limiting the benefit of allogeneic hematopoietic cell transplantation (HCT). Peripheral blood gene expression profiling of the donor immune repertoire following HCT may provide associated genes and pathways thereby improving the pathophysiologic understanding of chronic GVHD. We profiled 70 patients and identified candidate genes that provided mechanistic insight in the biologic pathways that underlie chronic GVHD. Our data revealed that the dominant gene signature in patients with chronic GVHD represented compensatory responses that control inflammation and included the interleukin-1 decoy receptor, IL-1 receptor type II, and genes that were profibrotic and associated with the IL-4, IL-6 and IL-10 signaling pathways. In addition, we identified three genes that were important regulators of extracellular matrix. Validation of this discovery phase study will determine if the identified genes have diagnostic, prognostic or therapeutic implications. (C) 2013 Elsevier Inc. All rights reserved.
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