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

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

PROVIDER: PRJNA559525 | ENA |

REPOSITORIES: ENA

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

Project description: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.

2019-09-11 | GSE135635 | GEO

IgG Autoantigen Array using sera from primary Sjogren's syndrome patients and non-Sjogren's syndrome controls

Project description:Sera were acquired from the Sjogren's International Collaborative Clinical Alliance (SICCA) biorepository and were assayed for IgG autoantibodies. The autoantigen array was performed to identify the specific autoantibodies that were enriched in pSS patients.

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Viral Profiles in Sjogren's Syndrome

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Project description:The study aims to investigate the relevance of NKp30 receptor in the salivary glands inflammation of Sjogren’s syndrome patients in comparison to sicca patients (control group) analysing the transcriptomic profile of salivary gland tissues.

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RNA-sequencing of human salivary gland from Sjogren's syndrome and sicca patients

Project description:RNA-sequencing of human salivary gland from Sjogren's syndrome and sicca patients

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Transcriptomic analysis of B cells from patients with Sjögren’s Syndrome

Project description:Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands and prominent B cell hyperactivity. B cells are crucial in the pathophysiology of pSS through several mechanisms, including cytokine production, exocrine gland destruction, and autoantibody secretion. Considering the central role of B cells we performed RNA-sequencing analysis of circulating CD19+ B cells from patients with pSS, non-Sjögren’s sicca (nSS), and healthy controls (HC).

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Transcriptome analysis of CCR9+, CXCR5+ and CCR9-CXCR5- Th cells in primary Sjögren's syndrome (pSS) patients and healthy controls (HC)

Project description:CCR9+ Tfh-like pathogenic T helper (Th) cells are elevated in patients with primary Sjögren’s syndrome (pSS) and indicated to play a role in pSS immunopathology. CCR9+, CXCR5+ and CCR9-CXCR5- (double negative, DN) Th cells from blood of 7 healthy controls (HC) and 7 pSS patients were FACS sorted and RNA sequencing was performed. Our aim is to delineate the CCR9+ Th cell-specific transcriptome to study the molecular dysregulation of these cells in pSS patients. Transcriptomic analysis of circulating CCR9+ Th cells reveals CCR9-specific pathways involved in effector T cell function, equally expressed in pSS patients and HC. Given the increased numbers of CCR9+ Th cells in the blood and inflamed glands of pSS patients and presence of inflammatory stimuli to activate these cells this suggests that CCR9-specific functions, such as cell recruitment upon CCL5 secretion, could significantly contribute to immunopathology in pSS.

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The transcriptome of paired major and minor salivary gland tissue in patients with primary Sjögren's syndrome

Project description:While all salivary glands (SGs) can be involved in primary Sjögren’s syndrome (pSS), their respective role in pathogenesis remains unclear. To assess immunopathway activation in paired parotid and labial gland tissue from biopsy-positive and biopsy-negative pSS and non-SS sicca patients, paraffin-embedded, paired parotid and labial salivary gland tissue and peripheral blood mononuclear cells were obtained from 39 pSS and 20 non-SS sicca patients. The patients were subdivided based on fulfillment of ACR-EULAR criteria and histopathology and the samples were analyzed for differentially expressed genes (DEGs). The principal component analysis of SG gene expression could only separate biopsy-positive pSS from non-SS sicca patients. However, when comparing the transcriptome of biopsy-positive pSS and biopsy-negative non-SS sicca patients, 1235 and 624 DEGs (FDR<-1 or >1) were identified for parotid and labial glands, respectively. The number of DEGs between biopsy negative pSS and non-SS sicca patients was scarce. The overall, transcript expression levels correlated strongly between parotid and labial glands (R2=0.86, p‐value<0.0001). Gene signatures present in both glands of biopsy‐positive pSS patients included IFN‐α signaling, IL-12/IL-18 signaling, CD3/CD28 T-cell activation, CD40 signaling in B-cells, DN2 B-cells, and FcRL4+ B-cells. Signature scores varied considerably amongst pSS patients. In conclusion, the transcriptomes of paired major and minor SGs in pSS were overall comparable, although significant inter-individual heterogeneity in immunopathway activation existed. The SG transcriptome of biopsy-negative pSS was indistinguishable from non-SS sicca patients. The different patterns of SG immunopathway activation in pSS argue for personalized treatment approaches.

2022-07-16 | GSE208260 | GEO

The transcriptome of paired major and minor salivary gland tissue in patients with primary Sjögren's syndrome

2021-05-05 | GSE173808 | GEO

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