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Immature cell populations and an erythropoiesis gene expression signature in systemic juvenile idiopathic arthritis: Implications for pathogenesis

ABSTRACT: Objective. Previous observations suggest that active systemic juvenile idiopathic arthritis (sJIA) is associated with a prominent erythropoiesis gene expression signature. The aim of this study was to determine the association of this signature with peripheral blood mononuclear cell (PBMC) subpopulations and its specificity for sJIA as compared to related conditions. 125 patients with JIA (18 sJIA and 107 non-sJIA) and 29 controls were studied. PBMC were isolated and analyzed for multiple surface antigens by flow cytometry and for gene expression profiles. The proportions of different PBMC subpopulations were compared among sJIA, non-sJIA patients and controls and subsequently correlated with the strength of the erythropoiesis signature. Additional gene expression data from patients with familial hemophagocytic lymphohistiocytosis (FHLH) and from a published sJIA cohort were analyzed to determine if the erythropoiesis signature was present. Keywords: Patient Vs Control, reassassment of phenotype

ORGANISM(S): Homo sapiens

PROVIDER: GSE21521 | GEO | 2010/06/25

SECONDARY ACCESSION(S): PRJNA125963

REPOSITORIES: GEO

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Project description:Objective. To identify gene expression differences in peripheral blood from patients with early and late onset juvenile idiopathic arthritis (JIA). Methods. Peripheral blood mononuclear cells (PBMC) were isolated from 56 healthy controls and 104 patients with recent onset JIA (39 persistent oligoarticular, 45 RF-polyarticular, and 20 systemic). Poly(A) RNA was amplified and labeled using NuGEN Ovation, and gene expression assessed with Affymetrix HG-U133 Plus 2.0 GeneChips®. Results. A total of 832 probe sets revealed gene expression differences (false-discovery rate 5%) in PBMC from children with oligoarticular JIA whose disease began before 6 years of age (age at onset [AaO] <6; early onset), compared to subjects whose disease began at 6 years of age or later (AaO ?6; late onset). In early onset patients there was greater expression of genes related to B-cells, and lesser expression of genes related to cells of the myeloid lineage. Support Vector Machine algorithms identified samples from early or late onset oligoarticular (97% accuracy) or polyarticular (89% accuracy) JIA patients, but not systemic JIA patients or healthy controls. Principal component analysis showed that the major classifier of samples was AaO regardless of whether they had oligoarticular or polyarticular JIA. Conclusion. PBMC gene expression analysis reveals biologic differences between early and late onset JIA patients independent of classification based on the number of joints involved. These data suggest AaO may be an important parameter to consider in JIA classification. Furthermore, different pathologic mechanisms may influence AaO, and understanding these processes may lead to improved treatment of JIA. Methods. Peripheral blood mononuclear cells (PBMC) were isolated from 56 healthy controls and 104 patients with recent onset JIA (39 persistent oligoarticular, 45 RF-polyarticular, and 20 systemic). Poly(A) RNA was amplified and labeled using NuGEN Ovation, and gene expression assessed with Affymetrix HG-U133 Plus 2.0 GeneChips®.

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Immature cell populations and an erythropoiesis gene expression signature in systemic juvenile idiopathic arthritis: Implications for pathogenesis

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