The Journal of Experimental Medicine
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Published online August 27, 2007
doi:10.1084/jem.20070070
The Journal of Experimental Medicine, Vol. 204, No. 9, 2131-2144
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Allantaz et al.
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ARTICLE

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

Florence Allantaz1,2, Damien Chaussabel1,2, Dorothee Stichweh1,2, Lynda Bennett1,2, Windy Allman1,2, Asuncion Mejias3, Monica Ardura3, Wendy Chung3, Carol Wise5, Karolina Palucka1,2, Octavio Ramilo3, Marilynn Punaro4,5, Jacques Banchereau1,2, and Virginia Pascual1,2,5

1 Baylor National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense, Dallas, TX 75204
2 Baylor Institute for Immunology Research, Dallas, TX 75204
3 Division of Pediatric Infectious Diseases and 4 Division of Pediatric Rheumatology, UT Southwestern Medical Center, Dallas, TX 75390
5 Texas Scottish Rite Hospital, Dallas, TX 75219

CORRESPONDENCE Virginia Pascual: Virginip{at}Baylorhealth.edu OR Jacques Banchereau: Jacquesb{at}Baylorhealth.edu OR Damien Chaussabel: Damienc{at}Baylorhealth.edu

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.

Abbreviations used: CLIC-2, chloride intracellular channel 2; JIA, juvenile idiopathic arthritis; mDC, myeloid DC; pDC, plasmacytoid DC; SLE, systemic lupus erythematosus; SoJIA, systemic onset JIA.

F. Allantaz and D. Chaussabel contributed equally to this work.


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