Division of Hematology/Oncology, Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Bone Marrow Transplant. 2013 Jun;48(6):755-60. doi: 10.1038/bmt.2012.143. Epub 2012 Aug 6.
Acute GVHD remains an important complication after allogeneic hematopoietic cell transplantation (HCT). Many efforts have been devoted to identifying potential noninvasive peripheral blood biomarkers to help improve the diagnosis or management of acute GVHD while avoiding invasive tissue biopsies. Early attempts to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF-α, however, both of these and others were not specific for GVHD, often being elevated in the setting of generalized inflammation, accompanying other major complications of HCT as well. More recent efforts have focused on additional cytokines and other cell-surface molecules, which function in leukocyte trafficking and activation with the hope that these can also serve as targets for novel therapeutic approaches. Modern proteomic methods have allowed the screening of large numbers of patient samples and yielded several novel candidate biomarkers, including elafin and reg3α, which may not be directly involved in the immunological pathogenesis of GVHD, but may be unique biomarkers for end-organ injury. Combining these new molecules with traditionally identified cytokines to form an acute GVHD biomarker panel has recently shown the ability to predict outcomes in patients who develop acute GVHD. The ultimate goals of identifying a specific biomarker are to refine diagnosis, guide therapy and develop risk-adapted approaches in order to better treat patients and improve outcomes after allogeneic HCT. These approaches include differential treatment for patients who develop acute GVHD with a high-risk biomarker profile as well as pre-emptive therapy in patients after HCT prior to the development of symptoms. With the recent progress summarized below, these goals may soon be realized.
急性移植物抗宿主病（GVHD）仍然是异基因造血细胞移植（HCT）后的一个重要并发症。许多人致力于寻找潜在的非侵入性外周血生物标志物，以帮助改善急性 GVHD 的诊断或管理，同时避免进行有创的组织活检。早期识别生物标志物的尝试主要集中在炎症细胞因子上，尤其是白细胞介素 2（IL-2）或肿瘤坏死因子-α（TNF-α），然而，这些细胞因子以及其他细胞因子都不是急性 GVHD 的特异性标志物，它们往往在全身性炎症时升高，同时伴随着 HCT 的其他主要并发症。最近的研究重点则放在其他细胞因子和其他细胞表面分子上，这些分子在白细胞的迁移和激活中发挥作用，希望它们也可以作为新的治疗方法的靶点。现代蛋白质组学方法可以筛选大量患者样本，并产生了几个新的候选生物标志物，包括弹性蛋白酶抑制剂（elafin）和 REG3α，它们可能不直接参与 GVHD 的免疫发病机制，但可能是终末器官损伤的独特生物标志物。将这些新分子与传统上确定的细胞因子结合起来，形成急性 GVHD 生物标志物组合，最近已显示出能够预测发生急性 GVHD 的患者的结局。确定特定生物标志物的最终目标是改善诊断、指导治疗和制定风险适应治疗方法，以更好地治疗异基因 HCT 后的患者并改善其结局。这些方法包括对具有高风险生物标志物特征的急性 GVHD 患者进行差异化治疗，以及在 HCT 后患者出现症状之前进行预防性治疗。下面总结了最近的进展，这些目标可能很快就会实现。
