A novel soluble form of Tim-3 associated with severe graft-versus-host disease.
A novel soluble form of Tim-3 associated with severe graft-versus-host disease.
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DOI：
10.1016/j.bbmt.2013.06.011
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发表时间：
2013-09
影响因子：
4.3
通讯作者：
McDonald, George B.
中科院分区：
文献类型：
--
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.
关键词：
T细胞Ig和粘蛋白结构域3 （Tim-3）受体被认为是适应性免疫反应的负调节因子。我们利用蛋白质组学策略鉴定异体造血细胞移植（HCT）后与移植物抗宿主病（GVHD）相关的新蛋白。与没有GVHD的受试者相比，中肠和上肠GVHD患者的血浆质谱分析发现，一种高可信度的蛋白质Tim-3水平升高。一项使用免疫测定法测量127例患者个体血浆样本中Tim-3水平的后续验证研究表明，与上肠GVHD患者（P = 0.005）、非GVHD患者（P = 0.002）和正常对照（P < 0.0001）相比，更严重的中肠GVHD患者的血浆Tim-3浓度显著更高。2 ~ 4级急性GVHD患者CD8+ T细胞表面Tim-3表达升高（P = 0.01）。对诊断为常见疾病的多名受试者的血浆质谱分析为GVHD背景下可溶性Tim-3的限制性释放提供了证据。这些发现对开发针对Tim-3免疫调节通路的新策略作为改善GVHD控制的方法具有机制意义。
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.
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影响因子：
30.5
作者：
Chiba, Shigeki;Baghdadi, Muhammad;Akiba, Hisaya;Yoshiyama, Hironori;Kinoshita, Ichiro;Dosaka-Akita, Hirotoshi;Fujioka, Yoichiro;Ohba, Yusuke;Gorman, Jacob V.;Colgan, John D.;Hirashima, Mitsuomi;Uede, Toshimitsu;Takaoka, Akinori;Yagita, Hideo;Jinushi, Masahisa
通讯作者：
Jinushi, Masahisa
DOI：
10.1084/jem.20060210
发表时间：
2006-06-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Koguchi K;Anderson DE;Yang L;O'Connor KC;Kuchroo VK;Hafler DA
通讯作者：
Hafler DA
影响因子：
20.3
作者：
Hockenbery, David M.;Cruickshank, Scott;McDonald, George B.
通讯作者：
McDonald, George B.
DOI：
10.1084/jem.20082429
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hafler DA;Kuchroo V
通讯作者：
Kuchroo V
影响因子：
4.4
作者：
Faca, Vitor;Pitteri, Sharon J.;Hanash, Samir
通讯作者：
Hanash, Samir