Specific gene expression profiles in systemic juvenile idiopathic arthritis
Specific gene expression profiles in systemic juvenile idiopathic arthritis
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DOI：
10.1002/art.22644
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发表时间：
2007-06-01
影响因子：
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通讯作者：
Woo, Patricia
中科院分区：
文献类型：
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作者：
Ogilvie, Emma Mary;Khan, Arshad;Woo, Patricia
目标。系统性幼年特发性关节炎(JIA)的患者有关节炎、发烧和其他关节外的特征。这种疾病通常仍然很严重，使人虚弱。本研究的目的是比较活动期和非活动期系统性类风湿关节炎患者外周血单个核细胞(PBMC)的基因表达谱，以确定和更好地了解活动期疾病的原因。对9例活动期系统性类风湿关节炎(RA)和8例非活动期系统性JIA(JIA)患者的PBMC基因表达谱进行了检测。进行非监督聚类和显著性分析。我们将系统性类风湿性关节炎的资料与多关节类风湿性关节炎、慢性婴幼儿神经系统疾病、皮肤、关节综合征、川崎病和系统性红斑狼疮患者的资料进行比较，以确定疾病特异性基因。对阴性选择的B细胞、T细胞和单核细胞进行定量逆转录聚合酶链式反应。表达基因的无监督聚类导致了与患者的临床状态(活动和非活动疾病)相对应的两组，并且与他们的药物无关。共有286个基因在活动期疾病患者中显著上调，其中86%是系统性JIA的特异性基因。IL-6在单核细胞和B细胞表达，IL-10在单核细胞表达，单核细胞和T细胞表达细胞因子信号转导抑制物3。外周血单核细胞的基因表达谱确定了系统性JIA患者的疾病特异性基因。细胞类型分析应该能够进一步深入了解这种疾病的机制。
Objective. Patients with systemic juvenile idiopathic arthritis (JIA) have arthritis, quotidian fevers, and other extraarticular features. This disease often remains severe and debilitating. The purpose of this study was to compare gene expression profiles in peripheral blood mononuclear cells (PBMCs) from patients with active and inactive systemic RA to define and better understand the cause of active disease.Methods. Gene expression profiles of PBMCs were determined in cells from 9 patients with active systemic RA and 8 patients with inactive systemic JIA. Unsupervised clustering and significance analysis were performed. We compared the systemic RA profile with data from patients with polyarticular RA, chronic infantile neurologic, cutaneous, articular syndrome, Kawasaki disease, and systemic lupus erythematosus to identify disease-specific genes. Quantitative reverse transcription-polymerase chain reaction of selected genes was performed on negatively selected B cells, T cells, and monocytes.Results. Unsupervised clustering of expressed genes resulted in 2 groups that corresponded to the clinical status of the patients (active and inactive disease) and was independent of their medications. A total of 286 genes were identified as significantly upregulated in patients with active disease and 86% of them were specific to systemic JIA. Interleukin-6 (IL-6) was expressed in monocytes and B cells, IL-10 in monocytes, and suppressor of cytokine signaling 3 in monocytes and T cells from patients with active disease.Conclusion. Gene expression profiles in PBMCs identified disease-specific genes in patients with systemic JIA. Cell type analyses should allow further insight into the mechanisms of the disease.