Background/Purpose:  Plasmacytoid dendritic cells (pDCs) are indicated to be key players in the pathogenesis of primary Sjögren’s syndrome (pSS) and important producers of type-1 interferon (IFN). This is based on their increased presence in pSS salivary glands, potential role in experimental animal models and the presence of an IFN signature in pSS patients, which is associated with disease activity measures. MicroRNAs are key regulators of cellular function and play a pivotal role in cellular function. To study potential dysregulation of pDCs of pSS patients, we investigated the expression of micro-RNAs (miRNA) in these cells in patients with pSS.

Methods:   Two independent cohorts (discovery and validation) were established including a total of 30 pSS patients who were classified according to the 2002 criteria. 15 healthy controls (HC) were included as control group and divided over the two cohorts. CD304-expressing cells were isolated from peripheral blood using MACS and profiling of 758 miRNA was performed using the OpenArray platform. miRNAs found to be differentially expressed in the discovery cohort (p<0.05, with at least a difference between the groups of log2) were subsequently measured in an independent validation cohort using a custom made array. Experimentally supported targets of validated miRNAs were used to perform pathway enrichment in order to assess the functional role of the dysregulated miRNAs.

Results:  Twenty-four miRNAs were significantly downregulated in pSS patients versus HC in the discovery cohort. 15 of these miRNAs were selected to be measured in the validation cohort, of which ten miRNAs were subsequently validated (p<0.05). Pathway enrichment indicated that these miRNAs are mainly involved in regulation of growth factor signalling and cell cycle (FDR corrected, p<0.05). We are currently studying the involvement of these miRNAs in pDC function and their correlation with their experimentally supported targets.  

Conclusion:  Ten miRNAs are expressed at lower levels in pDCs of patients with pSS as compared to healthy controls. Considering the potential of miRNAs in regulation of cell function, these data suggest a significant contribution to pDC function of miRNA dysregulation. Further analysis of the pathways in which these miRNAs are involved will expand our understanding on the role of pDCs in pSS.

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-expression-of-ten-micro-rnas-in-plasmacytoid-dendritic-cells-of-patients-with-primary-ss-indicates-dysregulation-on-multiple-levels/