Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 19, Issue 9, Pages 1323-1330Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2013.06.011
Keywords
TIM-3; Proteomics; Marrow transplantation; Hematopoietic cell transplantation; Graft-versus-host disease
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Funding
- National Institutes of Health (NIH) [AI33484, CA18029, CA15704, HL094260]
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The T cell Ig and mucin domain 3 (Tim-3) receptor has been implicated as a negative regulator of adaptive immune responses. We have utilized a proteomic strategy to identify novel proteins associated with graft versus host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Mass spectrometry analysis of plasma from subjects with mid-gut and upper-gut GVHD compared with those without GVHD identified increased levels of a protein identified with high confidence as Tim-3. A follow-up validation study using an immunoassay to measure Tim-3 levels in individual plasma samples from 127 patients demonstrated significantly higher plasma Tim-3 concentrations in patients with the more severe mid-gut GVHD, compared with those with upper-gut GVHD (P = .005), patients without GVHD (P = .002), and normal controls (P < .0001). Surface expression of Tim-3 was increased on CD8(+) T cells from patients with grade 2 to 4 acute GVHD (P = .01). Mass spectrometry based profiling of plasma from multiple subjects diagnosed with common diseases provided evidence for restricted release of soluble Tim-3 in the context of GVHD. These findings have mechanistic implications for the development of novel strategies for targeting the Tim-3 immune regulatory pathway as an approach to improving control of GVHD. (C) 2013 American Society for Blood and Marrow Transplantation.
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