Koczan Dirk, Guthke Reinhard, Thiesen Hans-Jürgen, Ibrahim Saleh M, Kundt Günther, Krentz Helga, Gross Gerd, Kunz Manfred
Institute of Immunology, University of Rostock, Schillingallee 70, 18055 Rostock, Germany.
Eur J Dermatol. 2005 Jul-Aug;15(4):251-7.
In the present report gene expression profiling of peripheral blood mononuclear cells (PBMC) from psoriasis patients suffering from severe generalized disease was performed comparing diseased stage with cured stage. By this means, 18 genes were identified which showed differential expression. The most significant differences were found for IL-8, annexin A3, cycloxygenase-2 (COX-2), cell cycle regulator G0S2, and pre-B cell enhancing factor (PBEF), all of which showed upregulation in the diseased stage. Microarray data were confirmed by real-time RT-PCR. Further analyses using support vector machines identified three pairs of genes (IL-8 - CDKN1C/p57, cyclooxygenase-2 - NR1D2, and desmocollin-2 - CDKN1C/p57) which allowed an accuracy of disease stage prediction of 86%, based on gene expression patterns. Taken together, this is the first large-scale gene expression study of psoriasis PBMC identifying candidate genes that might contribute to psoriasis immunopathogenesis. The genes identified in the present report and the molecular mechanisms underlying their regulation might serve as future targets for therapeutic intervention in psoriasis.
在本报告中,对患有严重全身性疾病的银屑病患者外周血单核细胞(PBMC)进行了基因表达谱分析,比较了疾病期和治愈期。通过这种方法,鉴定出18个显示差异表达的基因。在白细胞介素-8(IL-8)、膜联蛋白A3、环氧化酶-2(COX-2)、细胞周期调节因子G0S2和前B细胞增强因子(PBEF)中发现了最显著的差异,所有这些基因在疾病期均上调。微阵列数据通过实时逆转录聚合酶链反应(RT-PCR)得到证实。使用支持向量机的进一步分析鉴定出三对基因(IL-8 - CDKN1C/p57、环氧化酶-2 - NR1D2和桥粒芯蛋白-2 - CDKN1C/p57),基于基因表达模式,其疾病期预测准确率为86%。综上所述,这是首次对银屑病PBMC进行的大规模基因表达研究,鉴定出可能有助于银屑病免疫发病机制的候选基因。本报告中鉴定出的基因及其调控的分子机制可能成为未来银屑病治疗干预的靶点。