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Gene expression in active systemic JIA after anti-IL1 and anti-IL6R treatment
Pediatric Rheumatology volume 6, Article number: P28 (2008)
We have previously found specific genes upregulated in PBMCs of active sJIA . Biologics to block IL-1 and IL-6 signalling have both been shown to be effective in early clinical trials. In this study we examine the expression before and after anti-IL1 and anti IL-6R treatment in PBMCs and their constitutive cell types; using gene expression analysis to further understand the disease pathways.
PBMCs were collected before and after treatment from patients that responded to treatment: two patients were treated with tocilizumab, one with anakinra and another with an experimental anti-IL1 antibody (Novartis). A proportion of PBMCs were reserved and positive selection of B cells, T cells and monocytes performed on the rest. RNA was extracted and hybridised to Affymetrix U133 Plus 2.0 arrays. Paired significance analysis was performed using LIMMA.
In the B cell population we found 1902 genes differentially expressed after anti-IL1 treatment and 165 after anti-IL6R treatment. While genes involved in transcriptional regulation and the immune response were differentially expressed after both treatments there were only 24 genes that were common to both lists including TCL1A and CD69. Differential expression unique to the anti-IL1 blockade included downregulation of complement-mediated immunity genes e.g. CD55. Other genes downregulated after anti-IL1 include IL12RB2, and CREB1. Genes upregulated after anti-IL6R treatment include CEBPδ and BTLA. We are currently characterising gene expression in the remaining cell types.
We have found that the majority of changes in gene expression in B cells differ according to the specific cytokine modulation.
Ogilvie EM, Khan A, Hubank M, Kellam P, Woo P: Specific gene expression profiles in systemic juvenile idiopathic arthritis. Arthritis Rheum. 2007, 56: 1954-65. 10.1002/art.22644.
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Ogilvie, E., Samuel, J. & Woo, P. Gene expression in active systemic JIA after anti-IL1 and anti-IL6R treatment. Pediatr Rheumatol 6, P28 (2008) doi:10.1186/1546-0096-6-S1-P28
- Gene Expression
- Transcriptional Regulation
- Gene Expression Analysis
- Significance Analysis