Abstract
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.
Highlights
Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic disorders in children, with an incidence of 9.66/million/year in the United Kingdom between 2000–2018 [1]
The result showed that the gene expression pattern of the merged dataset was mainly classified into Systemic JIA (sJIA) patients and healthy control subjects by disease state, regardless of the tissue source and/or the platform. (Figure S1)
We conducted a meta-analysis on the merged microarray dataset and detected differentially expressed genes (DEGs) by comparing the expression levels between the sJIA group and the control group
Summary
Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic disorders in children, with an incidence of 9.66/million/year in the United Kingdom between 2000–2018 [1]. SJIA accounts for a large percentage of mortality occurring in JIA patients, even though it is a rare subtype of JIA [6]. It has been reported that severe complications, such as macrophage activation syndrome (MAS), are associated with the high mortality rate of sJIA [6]. MAS is a life-threatening condition characterized by the excessive activation of T cells and macrophages, resulting in hepatosplenomegaly, lymphadenopathy, cytopenia, coagulopathy, serious liver disease, and kidney failure [7,8]. These fatal complications amplify the need to understand the underlying biological mechanisms of sJIA
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