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Biol Blood Marrow Transplant. 2013 Sep;19(9):1323-30. doi: 10.1016/j.bbmt.2013.06.011. Epub 2013 Jun 17.

A novel soluble form of Tim-3 associated with severe graft-versus-host disease.

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Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.


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.


Graft-versus-host disease; Hematopoietic cell transplantation; Marrow transplantation; Proteomics; TIM-3

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