A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis.
A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis.
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DOI：
10.1093/rheumatology/kel095
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发表时间：
2006-12
期刊：
影响因子：
5.5
通讯作者：
Peter Szodoray;Peter Szodoray;P. Alex;Mark Barton Frank;Mary Turner;Sean Turner;N. Knowlton;C. Cadwell;Igor Dozmorov;Yuhong Tang;Patrick C. Wilson;Roland Jonsson;M. Centola
中科院分区：
文献类型：
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作者：
Peter Szodoray;Peter Szodoray;P. Alex;Mark Barton Frank;Mary Turner;Sean Turner;N. Knowlton;C. Cadwell;Igor Dozmorov;Yuhong Tang;Patrick C. Wilson;Roland Jonsson;M. Centola
目的类风湿关节炎(RA)被认为是一种典型的自身免疫性疾病，但B细胞在RA发病机制中的作用尚未完全阐明。方法对RA患者和对照组外周血B细胞进行基因芯片表达谱分析。使用差异基因表达分析和‘基因网络’分析(描述功能上相互关联的基因簇)来分析数据，以确定调控基因及其参与的途径。结果通过实时定量聚合酶链式反应和10种参与鉴定途径的血清细胞因子水平的测定得到证实。结果调控和影响细胞周期、增殖、凋亡、自身免疫、细胞因子网络、血管生成和神经免疫调节的基因在RA B细胞中有差异表达。此外，在这组RA患者中，调节这些通路的几种可溶性因子，包括IL-1β、IL-5、IL-6、IL-10、IL-12p40、IL-17和血管内皮生长因子的水平显著升高。结论B细胞在RA发病机制中的作用是多方面的，其中RA免疫失调调节B细胞生物学，从而促进致病性体液免疫反应的诱导和持续。
OBJECTIVE While rheumatoid arthritis (RA) is considered a prototypical autoimmune disease, the specific roles of B-cells in RA pathogenesis is not fully delineated. METHODS We performed microarray expression profiling of peripheral blood B-cells from RA patients and controls. Data were analysed using differential gene expression analysis and 'gene networking' analysis (characterizing clusters of functionally inter-relelated genes) to identify both regulatory genes and the pathways in which they participate. Results were confirmed by quantitative real-time polymerase chain reaction and by measuring the levels of 10 serum cytokines involved in the pathways identified. RESULTS Genes regulating and effecting the cell-cycle, proliferation, apoptosis, autoimmunity, cytokine networks, angiogenesis and neuro-immune regulation were differentially expressed in RA B-cells. Moreover, the serum levels of several soluble factors that modulate these pathways, including IL-1beta, IL-5, IL-6, IL-10, IL-12p40, IL-17 and VEGF were significantly increased in this cohort of RA patients. CONCLUSIONS These results outline aspects of the multifaceted role B-cells play in RA pathogenesis in which immune dysregulation in RA modulates B-cell biology and thereby contributes to the induction and perpetuation of a pathogenic humoral immune response.