Unknown,Transcriptomics,Genomics,Proteomics

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Blood Leukocyte Microarrays to Diagnose Systemic Onset Juvenile Idiopathic Arthritis and Follow IL-1 blocade


ABSTRACT: Systemic onset Juvenile Idiopathic Arthritis (SoJIA) represents up to 20% of Juvenile Idiopathic Arthritis (JIA). We have previously reported that this disease is Interleukin 1 (IL1)-mediated, and that IL-1 blockade results in clinical remission in the majority of patients. The diagnosis of SoJIA, however, still relies on clinical findings as no specific diagnostic tests are available, which leads to delays in the initiation of specific therapy. To identify specific diagnostic markers, we analyzed gene expression profiles in 19 pediatric patients with SoJIA during the systemic phase of the disease (fever and/or arthritis), 25 SoJIA patients with no systemic symptoms (arthritis only or no symptoms), 39 healthy controls, 94 pediatric patients with acute viral and bacterial infections (available under GSE6269), 38 pediatric patients with Systemic Lupus Erythematosus (SLE), and 6 patients with a second IL-1 mediated disease known as PAPA syndrome. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared to healthy children. These genes, however, were also changed in patients with acute infections and SLE. By performing an analysis of significance across all diagnostic groups, we generated a list of 88 SoJIA-specific genes (p<0.01 in SoJIA and >0.5 in all other groups). A subset of 12/88 genes permitted us to accurately classify an independent test set of SoJIA patients with systemic disease. We were also able to identify a group of transcripts that changed significantly in patients undergoing IL-1 blockade. Thus, analysis of transcriptional signatures from SoJIA blood leukocytes can help distinguishing this disease from other febrile illnesses and assessing response to therapy. Availability of accurate diagnostic markers for SoJIA patients may allow prompt initiation of effective therapy and prevention of long-term disabilities. Keywords: Disease state analysis 123 RNA samples extracted from PBMCs were studied. For more details on the clinical information, please refer to the paper (PudMed ID...).

ORGANISM(S): Homo sapiens

SUBMITTER: Florence Allantaz 

PROVIDER: E-GEOD-8650 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Allantaz Florence F   Chaussabel Damien D   Stichweh Dorothee D   Bennett Lynda L   Allman Windy W   Mejias Asuncion A   Ardura Monica M   Chung Wendy W   Smith Elisabeth E   Wise Carol C   Palucka Karolina K   Ramilo Octavio O   Punaro Marilynn M   Banchereau Jacques J   Pascual Virginia V  

The Journal of experimental medicine 20070827 9


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  ...[more]

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