signature=3a37a8457df881b117c841ee7fb71136,[THU0027] MONOCYTE-SPECIFIC GENE SIGNATURES IN RHEUMATOID...

最新推荐文章于 2025-04-23 20:29:15 发布

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最新推荐文章于 2025-04-23 20:29:15 发布

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研究通过高纯度分离风湿性关节炎（RA）患者和正常供体的外周血单核细胞，并在低温条件下进行基因表达分析。结果显示，RA患者单核细胞中有260个基因表达显著不同，涉及细胞通讯、信号转导、转录、防御反应、凋亡和热休克等过程。这些发现表明RA中单核细胞的激活和炎症状态，为RA的靶向治疗提供新的线索。

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摘要：

Background: In rheumatoid arthritis (RA), monocytes are of central importance in the chronic inflammatory immune response. These cells may display diagnostic markers and provide insight into pathophysiological pathways in RA. Objectives: To identify characterisitic expression patterns in RA, highly purified peripheral blood monocytes were investigated. Methods: Monocytes from 5 normal donors (ND) and 6 patients with active RA were purified by erythrocyte lysis and CD14-positive selection at constant low temperature (4 °C), conditions to minimize in vitro induced artefacts. Gene expression was detected by Affymetrix HG U133A hybridization. Bioinformatic analysis included MAS5.0 image analysis, statistical methods (t-test; Mann-Whitney) and cluster analysis (Genes@Work). Results: Array analysis revealed about 50% present calls in ND or RA monocytes. MAS5.0 comparison expression analysis revealed 605 genes significantly changed in more than 50% of all RA versus ND pairwise comparisons. Statistical methods revealed 260 of these genes significantly different (p <0.05). Selection and reduction by fold changes above 1.6 and statistical methods reduced the number of differentially expressed genes to 152. This set of genes indicates for cellular processes involved in cell communication (cytokines, chemokines and their receptors), intracellular signalling, transcription, defense response, apoptosis and heat shock responses. Hierarchical cluster analysis based on these selected genes separated into two branches, one for ND and one for RA patients. Conclusion: Gene expression profiling of separated peripheral blood monocytes identified a characteristic gene pattern, which is involved in the activation of monocytes and clearly indicates for an inflammatory process in RA. These results will be compared to expression profiles in other inflammatory rheumatic diseases and further analysed for dominant pathophysiological pathways in search for new candidates of targeted therapy in RA.

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