Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis
Corresponding Author
Michael G. Barnes
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
William S. Rowe Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 4010, Cincinnati, OH 45229Search for more papers by this authorAlexei A. Grom
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorSusan D. Thompson
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorThomas A. Griffin
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorPaul Pavlidis
University of British Columbia, Vancouver, British Columbia, Canada
Search for more papers by this authorLukasz Itert
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorNdate Fall
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorDawn Paxson Sowders
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorClaas H. Hinze
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorBruce J. Aronow
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorLorie K. Luyrink
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorShweta Srivastava
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorNorman T. Ilowite
Albert Einstein College of Medicine, Bronx, New York
Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria from Abbott, Novartis, and Bristol-Myers Squibb (less than $10,000 each).
Search for more papers by this authorBeth S. Gottlieb
Schneider Children's Hospital, New Hyde Park, New York
Search for more papers by this authorJudyann C. Olson
Medical College of Wisconsin and Children's Research Institute, Milwaukee, Wisconsin
Search for more papers by this authorDavid D. Sherry
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Search for more papers by this authorDavid N. Glass
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorRobert A. Colbert
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Dr. Colbert has received honoraria from the Spondyloarthritis Research and Treatment Network (SPARTAN), the University of Rochester Medical Center, and Grand Rounds; Carolinas (2007) (less than $10,000 each).
Search for more papers by this authorCorresponding Author
Michael G. Barnes
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
William S. Rowe Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 4010, Cincinnati, OH 45229Search for more papers by this authorAlexei A. Grom
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorSusan D. Thompson
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorThomas A. Griffin
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorPaul Pavlidis
University of British Columbia, Vancouver, British Columbia, Canada
Search for more papers by this authorLukasz Itert
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorNdate Fall
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorDawn Paxson Sowders
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorClaas H. Hinze
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorBruce J. Aronow
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorLorie K. Luyrink
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorShweta Srivastava
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorNorman T. Ilowite
Albert Einstein College of Medicine, Bronx, New York
Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria from Abbott, Novartis, and Bristol-Myers Squibb (less than $10,000 each).
Search for more papers by this authorBeth S. Gottlieb
Schneider Children's Hospital, New Hyde Park, New York
Search for more papers by this authorJudyann C. Olson
Medical College of Wisconsin and Children's Research Institute, Milwaukee, Wisconsin
Search for more papers by this authorDavid D. Sherry
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
Search for more papers by this authorDavid N. Glass
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Search for more papers by this authorRobert A. Colbert
Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
Dr. Colbert has received honoraria from the Spondyloarthritis Research and Treatment Network (SPARTAN), the University of Rochester Medical Center, and Grand Rounds; Carolinas (2007) (less than $10,000 each).
Search for more papers by this authorAbstract
Objective
To identify differences in peripheral blood gene expression between patients with different subclasses of juvenile idiopathic arthritis (JIA) and healthy controls in a multicenter study of patients with recent-onset JIA prior to treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents.
Methods
Peripheral blood mononuclear cells (PBMCs) from 59 healthy children and 136 patients with JIA (28 with enthesitis-related arthritis [ERA], 42 with persistent oligoarthritis, 45 with rheumatoid factor [RF]–negative polyarthritis, and 21 with systemic disease) were isolated from whole blood. Poly(A) RNA was labeled using a commercial RNA amplification and labeling system (NuGEN Ovation), and gene expression profiles were obtained using commercial expression microarrays (Affymetrix HG-U133 Plus 2.0).
Results
A total of 9,501 differentially expressed probe sets were identified among the JIA subtypes and controls (by analysis of variance; false discovery rate 5%). Specifically, 193, 1,036, 873, and 7,595 probe sets were different in PBMCs from the controls compared with those from the ERA, persistent oligoarthritis, RF-negative polyarthritis, and systemic JIA patients, respectively. In patients with persistent oligoarthritis, RF-negative polyarthritis, and systemic JIA subtypes, up-regulation of genes associated with interleukin-10 (IL-10) signaling was prominent. A hemoglobin cluster was identified that was underexpressed in ERA patients but overexpressed in systemic JIA patients. The influence of JAK/STAT, ERK/MAPK, IL-2, and B cell receptor signaling pathways was evident in patients with persistent oligoarthritis. In systemic JIA, up-regulation of innate immune pathways, including IL-6, Toll-like receptor/IL-1 receptor, and peroxisome proliferator–activated receptor signaling, were noted, along with down-regulation of gene networks related to natural killer cells and T cells. Complement and coagulation pathways were up-regulated in systemic JIA, with a subset of these genes being differentially expressed in other subtypes as well.
Conclusion
Expression analysis identified differentially expressed genes in PBMCs obtained early in the disease from patients with different subtypes of JIA and in healthy controls, providing evidence of immunobiologic differences between these forms of childhood arthritis.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| ART_24601_sm_SupplementaryTable1.xls1.8 MB | Supplemental Table 1. All genes identified as differnetially expressed |
| ART_24601_sm_SupplementaryTable2.doc92 KB | Supplemental Table 2: Selected gene groups of interest |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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