CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease
CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease
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DOI：
10.1182/blood-2007-06-097287
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发表时间：
2008-04-15
期刊：
影响因子：
20.3
通讯作者：
Kokai, Yasuo
中科院分区：
文献类型：
--
作者：
Hori, Tsukasa;Naishiro, Yasuyoshi;Kokai, Yasuo
尽管移植物抗宿主病（GVHD）是造血干细胞移植（HSCT）的危及生命的并发症，但其目前的诊断主要取决于临床表现和侵入性活检。 GVHD 的特定生物标志物将有助于及早、准确地识别这种严重疾病。利用蛋白质组学，我们在小鼠模型中筛选了 GVHD 特异性的血浆蛋白。一个分子量为 8972 Da 的峰在 2 个诊断组（GVHD 和正常对照）中保留了区分值，在疾病中表达增加，在环孢素 A 治疗期间表达减少，并且在同基因移植中几乎检测不到。纯化和质量分析确定该分子为 CCL8，是一个大趋化因子家族的成员。在人类样本中，CCL8 的血清浓度与 GVHD 严重程度密切相关。所有非 GVHD 样品的含量均低于 48 pg/mL（平均值 +/- SE：22.5 +/- 5.5 pg/mL，范围：12.6-48.0 pg/mL，n = 7）。与此形成鲜明对比的是，CCL8 在 GVHD 血清中高度上调，范围为 52.0 至 333.6 pg/mL（平均值 +/- SE：165.0 +/- 39.8 pg/mL，n = 7）。引人注目的是，2 名患有严重致命性 GVHD 的患者的 CCL8 水平极高（333.6 和 290.4 pg/mL）。CCL8 是一种有前途的特异性血清标志物，可用于 GVHD 的早期和准确诊断。
Although graft-versus-host disease (GVHD) is a life-threatening complication of hematopoletic stem-cell transplantation (HSCT), its current diagnosis depends mainly on clinical manifestations and invasive biopsies. Specific biomarkers for GVHD would facilitate early and accurate recognition of this grave condition. Using proteomics, we screened for plasma proteins specific for GVHD in a mouse model. One peak with 8972-Da molecular mass (m/z) retained a discriminatory value in 2 diagnostic groups (GVHD and normal controls) with increased expression in the disease and decreased expression during cyclosporin A treatment, and was barely detectable in syngeneic transplantation. Purification and mass analysis identified this molecule as CCL8, a member of a large chemokine family. In human samples, the serum concentration of CCL8 correlated closely with GVHD severity. All non-GVHD samples contained less than 48 pg/mL (mean +/- SE: 22.5 +/- 5.5 pg/mL, range: 12.6-48.0 pg/mL, n = 7). In sharp contrast, CCL8 was highly up-regulated in GVHD sera ranging from 52.0 to 333.6 pg/mL (mean +/- SE: 165.0 +/- 39.8 pg/mL, n = 7). Strikingly, 2 patients with severe fatal GVHD had extremely high levels of CCL8 (333.6 and 290.4 pg/mL. CCL8 is a promising specific serum marker for the early and accurate diagnosis of GVHD.