title: Whole blood expression profiling from the TREAT trial: insights for the pathogenesis of polyarticular juvenile idiopathic arthritis.
abstract: The Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT trial) was accompanied by a once-in-a-generation sample collection for translational research. In this paper, we report the results of whole blood gene expression analyses and genomic data-mining designed to cast light on the immunopathogenesis of polyarticular juvenile idiopathic arthritis (JIA).
  
  
  
  TREAT samples and samples from an independent cohort were analyzed on Affymetrix microarrays and compared to healthy controls. Data from the independent cohort were used to validate the TREAT data. Pathways analysis was used to characterize gene expression profiles. Furthermore, we correlated differential gene expression with new information about functional regulatory elements within the genome to develop models of aberrant gene expression in JIA.
  
  
  
  There was a strong concordance in gene expression between TREAT samples and the independent cohort. In addition, rheumatoid factor (RF)-positive and RF-negative patients showed only small differences on whole blood expression profiles. Analysis of the combined samples showed 158 genes represented by 176 probes that showed differential expression between TREAT subjects at baseline and healthy controls. None of the differentially expressed genes were encoded within linkage disequilibrium blocks containing single nucleotide polymorphisms known to be associated with risk for JIA. Functional analysis of these genes showed functional associations with multiple processes associated with innate and adaptive immunity, and appeared to reflect overall suppression of STAT1-3/interferon response factor-mediated pathways.
  
  
  
  Despite their limitations, whole blood expression profiles clearly distinguish children with polyarticular JIA from healthy controls. Whole blood expression profiles identify several immunologic pathways of biologic relevance that will need to be pursued in homogeneous cell populations in order to clarify mechanisms of pathogenesis.
  
  
  
  ClinicalTrials.gov registry #NCT00443430 , originally registered 2 March 2007 and last updated 30 May 2013.
authors.affiliation: Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Clinical & Translational Research Center, 875 Ellicott St., Buffalo, NY, USA.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Clinical & Translational Research Center, 875 Ellicott St., Buffalo, NY, USA.
authors.forename: Laiping
authors.initials: L
authors.lastname: Wong
authors.affiliation: Irving Cancer institute, Columbia University College of Physicians and Surgeons, 1130 Saint Nicholas Ave., New York, NY, 10032, USA.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Sawle
authors.affiliation: Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Program, 800 NE 13th St., Oklahoma City, OK, 73104, USA.
authors.forename: M Barton
authors.initials: MB
authors.lastname: Frank
authors.affiliation: Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Clinical & Translational Research Center, 875 Ellicott St., Buffalo, NY, USA.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Rheumatology, Seattle Children's Hospital and Research Institute, 4800 Sand Point Way NE, MA.7.110, Seattle, WA, 98105, USA.|Genetics, Genomics, and Bioinformatics Program, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wallace
authors.affiliation: Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Clinical & Translational Research Center, 875 Ellicott St., Buffalo, NY, USA. jamesjar@buffalo.edu.|Genetics, Genomics, and Bioinformatics Program, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA. jamesjar@buffalo.edu.
authors.forename: James N
authors.initials: JN
authors.lastname: Jarvis
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome
chemical_list: D018501:Antirheumatic Agents
keywords: Gene expression; Juvenile idiopathic arthritis; Microarray; Pathogenesis; Whole blood