A Novel Soluble Form of Tim-3 Associated with Severe Graft-versus-Host Disease

作者：Hansen John A^*; Hanash Samir M; Tabellini Laura; Baik Chris; Lawler Richard L; Grogan Bryan M; Storer Barry; Chin Alice; Johnson Melissa; Wong Chee Hong; Zhang Qing; Martin Paul J; McDonald George B

来源：Biology of Blood and Marrow Transplantation, 2013, 19(9): 1323-1330.

DOI：10.1016/j.bbmt.2013.06.011

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

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.

• 出版日期2013-9