Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade

被引:166
|
作者
Allantaz, Florence
Chaussabel, Damien [1 ]
Stichweh, Dorothee
Bennett, Lynda
Allman, Windy
Mejias, Asuncion
Ardura, Monica
Chung, Wendy
Wise, Carol
Palucka, Karolina
Ramilo, Octavio
Punaro, Marilynn
Banchereau, Jacques
Pascual, Virginia
机构
[1] Baylor Natl Inst Allergy & Infect Dis, Cooperat Ctr Translat Res Human Immunol & Biodef, Dallas, TX 75204 USA
[2] Baylor Inst Immunol Res, Dallas, TX 75204 USA
[3] UT SW Med Ctr, Div Pediat Infect Dis, Dallas, TX 75390 USA
[4] UT SW Med Ctr, Div Pediat Rheumatol, Dallas, TX 75390 USA
[5] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA
来源
JOURNAL OF EXPERIMENTAL MEDICINE | 2007年 / 204卷 / 09期
关键词
D O I
10.1084/jem.20070070
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2131 / 2144
页数:14
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