Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.

Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets.
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DOI:
10.1002/art.24534
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发表时间:
2009-07
影响因子:
--
通讯作者:
Glass, David N.
Glass, David N.
中科院分区:
其他
文献类型:
--
作者:
Griffin, Thomas A.;Barnes, Michael G.;Ilowite, Norman T.;Olson, Judyann C.;Sherry, David D.;Gottlieb, Beth S.;Aronow, Bruce J.;Pavlidis, Paul;Hinze, Claas. H.;Thornton, Sherry;Thompson, Susan D.;Grom, Alexei A.;Colbert, Robert A.;Glass, David N.

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基因芯片分析用于确定新近发病的儿童多关节幼年特发性关节炎(JIA)是否在外周血单个核细胞(PBMC)中表现出生物学或临床信息的基因表达特征。59名健康儿童和61名多关节JIA儿童在接受甲氨蝶呤或生物制剂等二线药物治疗前采集了外周血样本。从Ficoll分离的单个核细胞中提取RNA,荧光标记后与Affymetrix U133 Plus 2.0 GeneChips杂交。数据经过稳健的多阵列平均预处理和距离加权归一化处理后,以5%的错误发现率阈值使用方差分析进行分析。初步分析显示,在多关节JIA和对照组之间差异表达的基因有873个探针组。这些探针组的系统聚类区分了多关节JIA的三个亚组。每个亚组中的典型受试者被识别并用于定义亚组特有的基因表达特征。其中一个信号与单核细胞标记有关,另一个与转化生长因子β诱导基因有关,第三个与即刻早期基因有关。JIA亚组的基因表达特征与临床和生物学特征的相关性提示与疾病活动的各个方面有关,并支持将多关节JIA划分为不同的亚组。新近发病的多关节JIA的PBMC基因表达特征反映了离散的疾病过程,并提供了疾病的分子分类。
Microarray analysis was used to determine whether children with recent onset polyarticular juvenile idiopathic arthritis (JIA) exhibit biologically or clinically informative gene expression signatures in peripheral blood mononuclear cells (PBMC). Peripheral blood samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second-line medications, such as methotrexate or biological agents. RNA was extracted from Ficoll-isolated mononuclear cells, fluorescently labeled and hybridized to Affymetrix U133 Plus 2.0 GeneChips. Data were analyzed using ANOVA at a 5% false discovery rate threshold after Robust Multi-Array Average pre-processing and Distance Weighted Discrimination normalization. Initial analysis revealed 873 probe sets for genes that were differentially expressed between polyarticular JIA and controls. Hierarchical clustering of these probe sets distinguished three subgroups within polyarticular JIA. Prototypical subjects within each subgroup were identified and used to define subgroup-specific gene expression signatures. One of these signatures was associated with monocyte markers, another with transforming growth factor β-inducible genes, and a third with immediate-early genes. Correlation of gene expression signatures with clinical and biological features of JIA subgroups suggests relevance to aspects of disease activity and supports the division of polyarticular JIA into distinct subsets. PBMC gene expression signatures in recent onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease.
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