Systemic and cell type-specific gene expression patterns in scleroderma skin

Systemic and cell type-specific gene expression patterns in scleroderma skin
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DOI:
10.1073/pnas.1635114100
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发表时间:
2003-10-14
影响因子:
11.1
通讯作者:
Connolly, MK
Connolly, MK
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Whitfield, ML;Finlay, DR;Connolly, MK

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我们使用代表12,000个人类基因的DNA微阵列来表征皮肤活检组织中的基因表达模式,这些组织来自被诊断为系统性硬化症合并弥漫性硬皮病的个体。我们发现硬皮病患者的皮肤活检组织和正常、未受影响的患者的皮肤活检组织之间的基因表达模式一致不同。来自受影响个体的活检组织显示,在临床上受影响的组织和临床未受影响的组织中,基因表达的模式几乎无法区分,尽管这些模式与在类似组织中发现的非受影响个体的模式明显不同。在硬皮病和正常活检组织中,内皮细胞、B淋巴细胞和成纤维细胞中特有表达的基因有差异表达。通过免疫组织化学对硬皮病皮肤活检组织中淋巴细胞群的分析表明,我们阵列上观察到的B淋巴细胞特征来自CD20(+)B细胞。这些结果提供了硬皮病具有影响多种细胞类型的全身性表现的证据,并提示可以将基因作为该病的潜在标记。
We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20(+) B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease.