期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/ijms22020712
关键词
systemic juvenile idiopathic arthritis; meta-analysis; weighted gene co-expression network analysis (WGCNA); drug repositioning
资金
- National Research Foundation of Korea
- MSIT (Ministry of Science and ICT), Korea, under the ITRC (Information Technology Research Center) support program [IITP-2020-2020-0-01789]
- Ministry of Education
This study identified a robust sJIA signature consisting of 103 up-regulated genes and 25 down-regulated genes. Among these susceptibility genes, an up-regulated cluster of 11 genes and a down-regulated cluster of 4 genes were found to potentially play key roles in the pathogenesis of sJIA. Ten bioactive molecules targeting these significant gene clusters were identified as potential novel drug candidates for sJIA.
Systemic juvenile idiopathic arthritis (sJIA) is a rare subtype of juvenile idiopathic arthritis, whose clinical features are systemic fever and rash accompanied by painful joints and inflammation. Even though sJIA has been reported to be an autoinflammatory disorder, its exact pathogenesis remains unclear. In this study, we integrated a meta-analysis with a weighted gene co-expression network analysis (WGCNA) using 5 microarray datasets and an RNA sequencing dataset to understand the interconnection of susceptibility genes for sJIA. Using the integrative analysis, we identified a robust sJIA signature that consisted of 2 co-expressed gene sets comprising 103 up-regulated genes and 25 down-regulated genes in sJIA patients compared with healthy controls. Among the 128 sJIA signature genes, we identified an up-regulated cluster of 11 genes and a down-regulated cluster of 4 genes, which may play key roles in the pathogenesis of sJIA. We then detected 10 bioactive molecules targeting the significant gene clusters as potential novel drug candidates for sJIA using an in silico drug repositioning analysis. These findings suggest that the gene clusters may be potential genetic markers of sJIA and 10 drug candidates can contribute to the development of new therapeutic options for sJIA.
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