Ogilvie Emma Mary, Khan Arshad, Hubank Mike, Kellam Paul, Woo Patricia
University College London, London, UK.
Arthritis Rheum. 2007 Jun;56(6):1954-65. doi: 10.1002/art.22644.
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 JIA to define and better understand the cause of active disease.
Gene expression profiles of PBMCs were determined in cells from 9 patients with active systemic JIA and 8 patients with inactive systemic JIA. Unsupervised clustering and significance analysis were performed. We compared the systemic JIA profile with data from patients with polyarticular JIA, 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.
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 up-regulated 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.
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.
全身型幼年特发性关节炎（JIA）患者有关节炎、每日发热及其他关节外表现。这种疾病通常病情严重且使人衰弱。本研究的目的是比较活动期和非活动期全身型JIA患者外周血单个核细胞（PBMC）中的基因表达谱，以确定并更好地理解活动期疾病的病因。
测定了9例活动期全身型JIA患者和8例非活动期全身型JIA患者细胞中的PBMC基因表达谱。进行了无监督聚类和显著性分析。我们将全身型JIA的基因表达谱与多关节型JIA、慢性婴儿神经皮肤关节综合征、川崎病和系统性红斑狼疮患者的数据进行比较，以鉴定疾病特异性基因。对阴性分选的B细胞、T细胞和单核细胞进行了所选基因的定量逆转录-聚合酶链反应。
对表达基因进行无监督聚类，得到了与患者临床状态（活动期和非活动期疾病）相对应的2组，且与他们所服用的药物无关。共鉴定出286个在活动期疾病患者中显著上调的基因，其中86%为全身型JIA所特有。活动期疾病患者的单核细胞和B细胞中表达白细胞介素-6（IL-6），单核细胞中表达IL-10，单核细胞和T细胞中表达细胞因子信号传导抑制因子3。
PBMC中的基因表达谱鉴定出了全身型JIA患者的疾病特异性基因。细胞类型分析应能进一步深入了解该疾病的机制。
