Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood
Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood
复制标题
DOI：
10.1186/1744-9081-4-44
复制
发表时间：
2008-09-26
影响因子：
5.1
通讯作者：
Broderick, Gordon
中科院分区：
文献类型：
--
作者：
Aspler, Anne L.;Bolshin, Carly;Broderick, Gordon
背景资料：外周血基因组分析揭示了慢性疲劳综合征（CFS）的免疫改变，但在没有免疫人口背景下，解释仍然具有挑战性。这项工作的目的是确定特定的免疫功能成分的调制和重组的共表达网络的特点CFS使用的外周血quantitative genomics of peripheral blood.Methods：基因集构建了先验的CD4+ T细胞，CD8+ T细胞，CD19+ B细胞，CD14+单核细胞和CD16+中性粒细胞从公布的数据。一组111名妇女进行了分类，使用经验的情况下定义（美国）。S.疾病控制和预防中心）和无监督潜在聚类分析（LCA）。分析外周血的微阵列谱，用于白细胞特异性基因组的表达和从线性相关networks.Results的拓扑评估中鉴定的共表达的特征变化：在CD19+ B细胞中优先上调的一组6个基因的中值表达在CFS中显著较低（p = 0.01），主要是由于PTRA和TSPAN 3的表达。尽管没有其他基因组在p < 0.05时差异表达，但各组中的共表达模式显著不同。CD 14+单核细胞与CD 16+中性粒细胞的显著共表达（p = 0.01）和CD 19 + B细胞集（p = 0.00）表征了CFS和疲劳表型组。此外，在CFS中，CD8+和CD19+上调（p = 0.02）和NK基因集（p = 0.08）之间存在显著负相关。这些模式是不存在的controls.Conclusion：血液微阵列配置文件的解剖点B细胞功能障碍与协调的免疫激活支持持续的炎症和抗体介导的NK细胞调节T细胞活性。这具有临床意义，因为鉴定的CD19+基因可以为CFS的早期检测和明确的表型分型提供可靠的和生物学意义的基础。
Background: Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS) however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood.Methods: Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition ( U. S. Centers for Disease Control and Prevention) and unsupervised latent cluster analysis (LCA). Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks.Results: Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS p = 0.01) due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p < 0.05, patterns of co-expression in each group differed markedly. Significant co-expression of CD14+ monocyte with CD16+ neutrophil p = 0.01) and CD19+ B cell sets p = 0.00) characterized CFS and fatigue phenotype groups. Also in CFS was a significant negative correlation between CD8+ and both CD19+ up-regulated p = 0.02) and NK gene sets p = 0.08). These patterns were absent in controls.Conclusion: Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.