RNA-sequencing in plasmacytoid dendritic cells from patients with primary Sjogren's syndrome (pSS), non-Sjogren's sicca (nSS), and healthy donors (HC)

We here provide the first in-depth molecular analysis of pDCs from patients with pSS and nSS in comparison to HC. We isolated circulating pDCs from two independent cohorts of patients and controls (each n=31) and performed RNA-sequencing, after which data-driven networks and modular analysis were used to identify signatures of robustly reproducible transcriptional “signatures” of dysregulated differential and co-expressed genes. Four reproducible gene signatures were identified that indicated pDC activation. Comparison with in vitro activated pDCs showed that pSS pDCs have higher expression of many genes also upregulated upon pDC activation. In all transcriptional analyses, nSS patients formed an intermediate group in which some patients were molecularly similar to pSS patients. Our data provide in-depth characterization of the aberrant regulation of pDCs from patients with nSS and pSS and substantiate their perceived role in the immunopathology of pSS, supporting studies that target pDCs, type-I IFNs, or IFN-signalling in pSS. Overall design: RNA-sequencing in primary circulating plasmacytoid dendritic cells from patients with pSS, nSS, and HC. Two cohorts of n=31 each are included (discovery and replication), no duplicates samples