皮肤慢性移植物抗宿主病不具有系统性硬化症的异常内皮细胞表型或血管稀疏特征。
Cutaneous chronic graft-versus-host disease does not have the abnormal endothelial phenotype or vascular rarefaction characteristic of systemic sclerosis.
作者信息
Fleming Jo Nadine, Shulman Howard M, Nash Richard A, Johnson Pamela Y, Wight Thomas N, Gown Allen, Schwartz Stephen M
机构信息
Department of Pathology, University of Washington, Seattle, Washington, USA.
出版信息
PLoS One. 2009 Jul 9;4(7):e6203. doi: 10.1371/journal.pone.0006203.
BACKGROUND
The clinical and histologic appearance of fibrosis in cutaneous lesions in chronic graft-versus -host disease (c-GVHD) resembles the appearance of fibrosis in scleroderma (SSc). Recent studies identified distinctive structural changes in the superficial dermal microvasculature and matrix of SSc skin. We compared the dermal microvasculature in human c-GVHD to SSc to determine if c-GVHD is a suitable model for SSc.
METHODOLOGY/PRINCIPAL FINDINGS: We analyzed skin biopsies of normal controls (n = 24), patients with SSc (n = 30) and c-GVHD with dermal fibrosis (n = 133)). Immunostaining was employed to identify vessels, vascular smooth muscle, dermal matrix, and cell proliferation. C-GVHD and SSc had similar dermal matrix composition and vascular smooth muscle pathology, including intimal hyperplasia. SSc, however, differed significantly from c-GVHD in three ways. First, there were significantly fewer (p = 0.00001) average vessels in SSc biopsies (9.8) when compared with c-GVHD (16.5). Second, in SSc, endothelial markers were decreased significantly (19/19 and 12/14 for VE cadherin and vWF (p = <0.0001 and <0.05), respectively). In contrast, 0/13 c-GVHD biopsies showed loss of staining with canonical endothelial markers. Third, c-GVHD contained areas of microvascular endothelial proliferation not present in the SSc biopsies.
CONCLUSIONS/SIGNIFICANCE: The sclerosis associated with c-GVHD appears to resemble wound healing. Focal capillary proliferation occurs in early c-GVHD. In contrast, loss of canonical endothelial markers and dermal capillaries is seen in SSc, but not in c-GVHD. The loss of VE cadherin in SSc, in particular, may be related to microvascular rarefaction because VE cadherin is necessary for angiogenesis. C-GVHD is a suitable model for studying dermal fibrosis but may not be applicable for studying the microvascular alterations characteristic of SSc.
背景
慢性移植物抗宿主病（c-GVHD）皮肤病变中纤维化的临床和组织学表现类似于硬皮病（SSc）中的纤维化表现。最近的研究发现了SSc皮肤浅表真皮微血管和基质中独特的结构变化。我们比较了人类c-GVHD和SSc的真皮微血管，以确定c-GVHD是否是SSc的合适模型。
方法/主要发现：我们分析了正常对照（n = 24）、SSc患者（n = 30）和有皮肤纤维化的c-GVHD患者（n = 133）的皮肤活检样本。采用免疫染色来识别血管、血管平滑肌、真皮基质和细胞增殖。C-GVHD和SSc具有相似的真皮基质组成和血管平滑肌病理，包括内膜增生。然而，SSc在三个方面与c-GVHD有显著差异。首先，与c-GVHD（16.5）相比，SSc活检样本中的平均血管数量显著减少（p = 0.00001）（9.8）。其次，在SSc中，内皮标志物显著减少（VE钙黏蛋白和vWF分别为19/19和12/14，p = <0.0001和<0.05）。相比之下，13份c-GVHD活检样本中没有一份显示典型内皮标志物染色缺失。第三，c-GVHD含有SSc活检样本中不存在的微血管内皮增殖区域。
结论/意义：与c-GVHD相关的硬化似乎类似于伤口愈合。早期c-GVHD中出现局灶性毛细血管增殖。相比之下，SSc中可见典型内皮标志物和真皮毛细血管缺失，但c-GVHD中未见。特别是SSc中VE钙黏蛋白的缺失可能与微血管稀疏有关，因为VE钙黏蛋白是血管生成所必需的。C-GVHD是研究真皮纤维化的合适模型，但可能不适用于研究SSc特有的微血管改变。
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