Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis.
Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis.
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DOI：
10.1002/art.24601
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发表时间：
2009-07
影响因子：
--
通讯作者：
Colbert, Robert A.
中科院分区：
文献类型：
--
作者：
Barnes, Michael G.;Grom, Alexei A.;Thompson, Susan D.;Griffin, Thomas A.;Pavlidis, Paul;Itert, Lukasz;Fall, Ndate;Sowders, Dawn Paxson;Hinze, Claas H.;Aronow, Bruce J.;Luyrink, Lorie K.;Srivastava, Shweta;Ilowite, Norman T.;Gottlieb, Beth S.;Olson, Judyann C.;Sherry, David D.;Glass, David N.;Colbert, Robert A.
对新近发病的幼年特发性关节炎(JIA)患者在接受DMARDS或生物制剂治疗前进行了一项多中心研究，以确定JIA亚型和对照组之间外周血基因表达的差异。通过Ficoll分离了59名健康儿童和136名JIA受试者的PBMC(28名脊柱炎相关关节炎[ERA]，42名持续性少关节炎，45名RF多发性关节炎和21名全身性)。用NuGen Ovation标记Poly-A RNA，用Affymetrix HG-U133 plus 2.0阵列获得基因表达谱。在JIA亚型和对照中发现了9,501个差异表达的探针集(ANOVA，FDR 5%)。具体而言，在对照组和ERA、持续性少关节炎、RF多发性关节炎和系统性JIA样本中，分别有193、1036、873和7595个探针组不同。在持续性少关节炎、RF多发性关节炎和系统性JIA亚型中，与IL-10信号相关的基因上调显著。发现了一个在ERA患者中低表达但在系统性JIA中高表达的血红蛋白簇。JAK/STAT、ERK/MAPK、IL-2和B细胞受体信号通路在持续性少关节炎中的作用明显。在系统性JIA中，包括IL-6、TLR/IL1R和PPAR信号在内的天然免疫途径上调，而与NK和T细胞相关的基因网络下调。补体和凝血途径在系统性JIA中上调，这些基因的子集在其他亚型中也有差异表达。表达分析确定了早期JIA亚型和对照组PBMCs中差异表达的基因，从而为这些类型的儿童关节炎之间的免疫生物学差异提供了证据。
A multi-center study of recent onset juvenile idiopathic arthritis (JIA) subjects prior to treatment with DMARDS or biologics was undertaken to identify peripheral blood gene expression differences between JIA subclasses and controls. PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis [ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated over Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays. 9,501 differentially expressed probe sets were identified among JIA subtypes and controls (ANOVA, FDR 5%). Specifically, 193, 1036, 873 and 7595 probe sets were different between controls and ERA, persistent oligoarthritis, RF- polyarthritis and systemic JIA samples respectively. In persistent oligoarthritis, RF- polyarthritis and systemic JIA subtypes, up-regulation of genes associated with IL-10 signaling was prominent. A hemoglobin cluster was identified that was under-expressed in ERA patients but over-expressed in systemic JIA. The influence of JAK/STAT, ERK/MAPK, IL-2 and B cell receptor signaling pathways was evident in persistent oligoarthritis. In systemic JIA, up-regulation of innate immune pathways, including IL-6, TLR/IL1R, and PPAR signaling were noted, along with down-regulation of gene networks related to NK and T cells. Complement and coagulation pathways were up-regulated in systemic JIA with a subset of these genes differentially-expressed in other subtypes as well. Expression analysis identified differentially expressed genes in PBMCs between subtypes of JIA early in disease and controls, thus providing evidence for immunobiologic differences between these forms of childhood arthritis.
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影响因子：
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作者：
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作者：
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作者：
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