Whitfield Michael L, Finlay Deborah R, Murray John Isaac, Troyanskaya Olga G, Chi Jen-Tsan, Pergamenschikov Alexander, McCalmont Timothy H, Brown Patrick O, Botstein David, Connolly M Kari
Department of Dermatology, University of California-San Francisco, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12319-24. doi: 10.1073/pnas.1635114100. Epub 2003 Oct 6.
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.
我们使用代表超过12000个人类基因的DNA微阵列，来表征诊断为弥漫性硬皮病的系统性硬化症患者皮肤活检样本中的基因表达模式。我们发现，硬皮病患者的皮肤活检样本与正常未受影响个体的皮肤活检样本之间，基因表达模式存在一致差异。尽管硬皮病患者受影响组织和未受临床影响组织在临床上易于区分，但这些组织的活检样本显示出几乎难以区分的基因表达模式，不过它们与未受影响个体相似组织中的基因表达模式明显不同。在内皮细胞、B淋巴细胞和成纤维细胞中特征性表达的基因，在硬皮病活检样本和正常活检样本之间存在差异表达。通过免疫组织化学分析硬皮病皮肤活检样本中的淋巴细胞群体表明，我们阵列上观察到的B淋巴细胞特征来自CD20 + B细胞。这些结果提供了证据，表明硬皮病具有影响多种细胞类型的全身表现，并提示了可作为该疾病潜在标志物的基因。
