Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis Rheum 2009 Jul;60(7):2102-12

Date

07/01/2009

Pubmed ID

19565513

Pubmed Central ID

PMC2782469

DOI

10.1002/art.24601

Scopus ID

2-s2.0-67650066800   116 Citations

Abstract

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.

Author List

Barnes MG, Grom AA, Thompson SD, Griffin TA, Pavlidis P, Itert L, Fall N, Sowders DP, Hinze CH, Aronow BJ, Luyrink LK, Srivastava S, Ilowite NT, Gottlieb BS, Olson JC, Sherry DD, Glass DN, Colbert RA

Author

Judyann C. Olson MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Antirheumatic Agents
Arthritis
Arthritis, Juvenile
Case-Control Studies
Child
Child, Preschool
Female
Gene Expression Profiling
Gene Expression Regulation
Humans
Infant
Interleukin-6
Leukocytes, Mononuclear
Male
Peroxisome Proliferator-Activated Receptors
Receptors, Interleukin-1
Toll-Like Receptors
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280