Epidermal Elafin Expression Is an Indicator of Poor Prognosis in Cutaneous Graft-versus-Host Disease
Epidermal Elafin Expression Is an Indicator of Poor Prognosis in Cutaneous Graft-versus-Host Disease
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DOI：
10.1038/jid.2014.489
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发表时间：
2015-04-01
影响因子：
6.5
通讯作者：
Stary, Georg
中科院分区：
文献类型：
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作者：
Brueggen, Marie-Charlotte;Petzelbauer, Peter;Stary, Georg
移植物抗宿主病（GVHD）仍然是同种异体造血干细胞移植的常见且可能危及生命的并发症。在皮肤中，GVHD 可以急性 (aGVHD)、慢性苔藓样 (clGVHD) 或慢性硬化形式 (csGVHD) 形式存在。测量角质形成细胞来源的蛋白酶抑制剂elafin的外周血水平最近已成为诊断皮肤aGVHD的有前途的工具。我们评估了皮肤中elafin表达的分析是否能够区分aGVHD和药物过敏皮疹（DHR），以及皮肤elafin表达是否与疾病严重程度或aGVHD和clGVHD/csGVHD改变的预后相关。收集aGVHD (n = 22)、clGVHD (n = 15)、csGVHD (n = 7) 和DHR (n = 10) 患者的皮肤活检，并分析表皮elafin 表达及其与不同临床/组织学参数的关系。急性GVHD和DHR表现出不同程度的elafin表达。 csGVHD 中未检测到elafin，而与aGVHD 相比，clGVHD 中该分子有所增加。 Elafin 高 aGVHD/clGVHD 病变表现为表皮增厚，并与不良预后相关，即 aGVHD 中的总生存率降低和 clGVHD 中的皮质类固醇耐药性降低。尽管皮肤弹性蛋白似乎不能区分 aGVHD 和 DHR 病变，但我们的研究强烈表明皮肤弹性蛋白表达与皮肤 GVHD 患者的不良预后之间存在关联。
Graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. In the skin, GVHD can present in an acute (aGVHD), chronic lichenoid (clGVHD), or chronic sclerotic form (csGVHD). Measuring peripheral blood levels of the keratinocyte-derived protease inhibitor elafin has recently emerged as a promising tool for the diagnosis of cutaneous aGVHD. We evaluated whether the analysis of elafin expression in skin would allow distinguishing aGVHD from drug hypersensitivity rashes (DHR) and whether cutaneous elafin expression would correlate with disease severity or altered prognosis of aGVHD and clGVHD/csGVHD. Skin biopsies from aGVHD (n=22), clGVHD (n=15), csGVHD (n =7), and DHR (n =10) patients were collected and epidermal elafin expression and its association with diverse clinical/histological parameters were analyzed. Acute GVHD and DHR displayed varying degrees of elafin expression. No elafin was detectable in csGVHD, whereas the molecule was increased in clGVHD as compared with aGVHD. Elafin-high aGVHD/clGVHD lesions presented with epidermal thickening and were associated with poor prognosis-i.e., decreased overall survival in aGVHD and corticosteroid resistance in clGVHD. Although cutaneous elafin does not seem to discriminate aGVHD from DHR lesions, our study strongly suggests an association between cutaneous elafin expression and poor prognosis for patients with cutaneous GVHD.