Background/Purpose:  Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and dryness of mouth and eyes. Type-1 classical dendritic cells (cDCs) are very potent antigen presenting cells known to induce strong T-cell proliferation and cytokine production. Despite the fact that especially cDC1s are candidate key players in the activation of local T and B-cells in pSS, they have rarely been studied in pSS. Considering the critical role of micro-RNAs (miRNAs) in regulation of gene expression, we investigated miRNA expression in isolated cDC1s of patients with pSS.

Methods:  Two independent cohorts (discovery and validation) were established, consisting of 29 pSS patients who were classified according to the 2002 criteria. 17 healthy controls (HC) were included as control group. cD1c+ CD19- cells were isolated from peripheral blood using MACS and we performed miRNA profiling of 758 miRNA targets using the OpenArray platform in the donors included in the discovery cohort. A selection of 15 miRNAs found to be differentially expressed in the pSS group versus the control group (at p<0.05, with at least a difference between the groups of log2) was measured in the independent validation cohort using a custom made array. We performed pathway enrichment with the experimentally supported targets of the validated miRNAs to assess their function in these cells.

Results:  A total of 24 miRNAs were downregulated in pSS patients versus HC in the discovery cohort. Of these, 16 targets were selected for validation. Pathway enrichment showed that the experimentally supported targets of these miRNAs are mainly involved in growth-factor signalling and vesicle trafficking (p<0.05, FDR corrected). We are currently performing functional experiments in primary cells to dissect the effects of the dysregulated miRNA expression in these cells.

Conclusion:  miR-130a and miR708 are significantly downregulated in cDC1s of patients with pSS, which indicates dysregulation in a range of pathways that are involved in DC function. These are the first data from primary cells to indicate dysregulation of type-1 cDCs in this group of patients, urging for further assessment of these cells in future studies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-expression-of-micro-rna-130a-and-micro-rna-708-in-type-1-classical-dendritic-cells-of-patients-with-primary-ss-indicates-their-dysregulation/