Background/Purpose: Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease of childhood, and the predominant effector cells are mononuclear phagocytes rather than lymphocytes as in autoimmune diseases such as rheumatoid arthritis (RA).  Previous gene expression data has shown that monocytes in SJIA have a novel phenotype with clear proinflammatory activation as well as features of alternative activation.  This aberrant phenotype may contribute to the potential of these children to develop macrophage activation syndrome (MAS).  What controls monocyte/macrophage differentiation in SJIA is unknown.  MicroRNA are small, non-coding RNA that serve as transcriptional negative regulators to fine-tune gene expression programs involved in cell differentiation, metabolism and immunity.  There is growing evidence that miRNA contribute to the pathogenesis of human disease, including RA.  These regulators have also been implicated in controlling differentiation of monocytes and macrophages.  However, miRNA expression in SJIA has not been examined.  Here, we examine miRNA expression profiles in peripheral blood monocytes from children with SJIA.

Methods: We enrolled children with active SJIA, defined as presence of active arthritis or systemic features, as well as those with new-onset disease or clinically inactive disease (CID).  Freshly isolated CD14+ monocytes were isolated by magnetic beads separation, and used to generate RNA which in turn was used to quantitate the expression of 384 miRNA and controls on the TaqMan ™ MicroRNA Array A.

Results: We found that monocyte expression of mir-125a-5p was significantly elevated in children with active SJIA compared to those with CID (relative expression 16.8 vs. 3.0, p<0.05).  In addition, expression of mir-125a-5p was significantly correlated with markers of disease activity including ferritin (R=0.73, p<0.001) as well as presence of systemic features such as hepatosplenomegaly.  Recently miR-125a-5p has been suggested to play an essential role in monocyte polarization.  We also found several specific miRNA with differential expression in monocytes from children with new-onset disease compared to those with active established disease.  One of these, miR-187, has been implicated in negative regulation of inflammatory cytokines including IL-6.  We find that miR-187 expression strongly correlates with markers of disease activity including C-reactive protein (R=0.813, p<0.05), ferritin (R=0.644, p<0.05) and soluble IL-2 receptor (R=0.779, p<0.05) as well as presence of systemic features.  Interestingly, while monocyte expression of miR-146a has been correlated with disease activity in RA, we found no difference in expression between monocytes from patients with active SJIA and those with CID.

Conclusion: These results provide the first report of miRNA expression profiles in children with SJIA.  Taken together, these data suggest that differential miRNA expression contributes to the phenotype of monocyte/macrophages in SJIA, and may have implications for disease pathogenesis and development of MAS.  Further work will examine impact of miRNA expression on monocyte function and differentiation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/differential-expression-of-microrna-in-monocytes-from-children-with-systemic-juvenile-idiopathic-arthritis-implications-for-polarized-phenotype/