Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade.
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.
Allantaz
Florence
F
Baylor National Institute of Allergy and Infectious Diseases Cooperative Center for Translational Research on Human Immunology and Biodefense, Dallas, TX 75204, USA.
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
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001171:Arthritis, Juvenile / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics / Q000628:therapy; D016022:Case-Control Studies; D002648:Child; D018118:Chloride Channels / Q000235:genetics; D003141:Communicable Diseases / Q000235:genetics; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D006262:Health; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic / Q000187:drug effects
C108828:CLIC2 protein, human; D018118:Chloride Channels; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1