Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade
Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade
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DOI：
10.1084/jem.20070070
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发表时间：
2007-09-03
影响因子：
15.3
通讯作者：
Pascual, Virginia
中科院分区：
文献类型：
--
作者：
Allantaz, Florence;Chaussabel, Damien;Pascual, Virginia
系统性发作少年特发性关节炎（Sojia）代表多达20％的少年特发性关节炎。我们最近报道说，白介素（IL）1是该疾病的重要介体，IL-1阻断会导致临床缓解。但是，最初的全身表现缺乏特异性会导致诊断和开始治疗的延迟。为了开发特定的诊断测试，我们分析了44例儿科sojia患者的白细胞基因表达谱，94例急性病毒和细菌感染的小儿儿科患者，38例全身性红斑狼疮患者（SLE）患者（SLE），6例患有PAPA综合征的患者，以及39名健康的儿童。 。与健康儿童相比，统计组比较和类预测鉴定在索jia患者中差异表达的基因。但是，急性感染和SLE患者也改变了这些基因。对所有诊断组的显着性分析鉴定了88个Sojia特异性基因，其中12个准确地归类了一组独立的sojia患有全身性疾病的患者。还确定了在接受IL-1阻滞的患者中发生显着变化的转录本。因此，白细胞的转录特征可用于区分sojia和其他发热疾病并评估对治疗的反应。早期诊断标记的可用性可能允许迅速开始治疗和预防残疾。
Systemic onset juvenile idiopathic arthritis ( SoJIA) represents up to 20% of juvenile idiopathic arthritis. We recently reported that interleukin ( IL) 1 is an important mediator of this disease and that IL-1 blockade induces clinical remission. However, lack of specificity of the initial systemic manifestations leads to delays in diagnosis and initiation of therapy. To develop a specific diagnostic test, we analyzed leukocyte gene expression profiles of 44 pediatric SoJIA patients, 94 pediatric patients with acute viral and bacterial infections, 38 pediatric patients with systemic lupus erythematosus ( SLE), 6 patients with PAPA syndrome, and 39 healthy children. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared with healthy children. These genes, however, were also changed in patients with acute infections and SLE. An analysis of significance across all diagnostic groups identified 88 SoJIA-specific genes, 12 of which accurately classified an independent set of SoJIA patients with systemic disease. Transcripts that changed significantly in patients undergoing IL-1 blockade were also identified. Thus, leukocyte transcriptional signatures can be used to distinguish SoJIA from other febrile illnesses and to assess response to therapy. Availability of early diagnostic markers may allow prompt initiation of therapy and prevention of disabilities.