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Abstract
The presence of abnormal gene expression signatures is a well-described feature of the oligoarticular and polyarticular forms of juvenile idiopathic arthritis. In this review, we discuss how new insights into genetic risk for JIA and the three dimensional architecture of the genome may be used to develop a better understanding of the mechanisms driving these gene expression patterns.
Highlights
We have subsequently repeated this technique using all publically available gene expression data from children with oligoarticular and polyarticular juvenile idiopathic arthritis (JIA) and gotten the same result. This has led us to the conclusion that if genetic variants associated with JIA influence the observed transcriptional patterns, they must either do so within specific leukocyte subsets that are not detectable using whole blood, or they must act on longer-range chromatin interactions
Using RNA sequencing in human neutrophils, we have shown that the haplotype contains at least one non-coding intergenic RNA, a species of RNAs that are important in regulating both three dimensional chromatin architecture [43] and gene expression [44]
We have previously shown that the presence of non-coding intergenic RNA (ncRNA) molecules expressed in neutrophils is a common feature within the JIA risk loci [31, 32] and the presence of such RNA species in pathologically relevant cells is a characteristic that the JIA risk loci share with those of most other complex traits
Summary
TRANSCRIPTIONAL ABNORMALITIES IN JIA: LESSONS LEARNED FROM GENE EXPRESSION PROFILING. These transcriptional abnormalities can be observed in whole blood [12], unsorted white blood cells (buffy coats) [15], peripheral blood mononuclear cells (PBMC) [9, 16], neutrophils [17], and CD4+ T cells [18]. These studies have generally identified clusters of interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa) regulated genes that display differential expression in children with active polyarticular JIA when they are compared to healthy control children. This discussion will not be comprehensive, and the reader wishing to have a deeper understanding is invited to read the recent reviews available on this subject [26, 27]
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