Project description:Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by reduced activity of the exocrine glands (principally the salivary and lacrimal glands) due to chronic lymphocytic infiltration. pSS has been closely associated with an enhanced risk of mucosa-associated lymphoid tissue (MALT) lymphoma. However, the dynamic epigenetic changes in gland cells accompanied with this pathogenesis are not fully understood. In present study, the labial gland (LG) and parotid gland (PG) tissues from two pSS patients with lymphoma were harvested including LG with negative anti-SSA/SSB and LG with positive anti-SSA/SSB at the first diagnosis of pSS, as well as PG with and without lymphoma tissues at the second diagnosis of MALT. ChIP-seq of H3K4/9/27/36/79me3 were performed. This data is benefit to advanced understanding the dynamic development of MALT from pSS, emphasizing the importance of epigenetic alterations in regulating transcription during the pathologic process.
Project description:In this study, we aimed to identify a miRNA expression signature that could be used to distinguish PCa from BPH. We have shown for the first time in the literature the presence of miRNAs in the PSS. We suggest PSS as a powerful non-invasive source for evaluation of prognosis in PCa, since prostate massages can be easily applied during routine examination. Our results showed that certain differentially expressed miRNAs in PSS could be used as diagnostics markers.
Project description:Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by typical autoantibody production and lymphocytic-mediated exocrine gland damage. Interstitial lung disease (ILD) is a common complication of pSS and can be associated with a poor prognosis. However, the pathogenesis of ILD in pSS is still unclear. In this study, we used RNA sequencing to investigate the gene-expression profile of the minor salivary glands (MSGs) from 36 patients with ILD-pSS and 128 patients with non-ILD-pSS. In the remarkably enriched chemokine-mediated signaling pathway, CXCR2 was found to be significantly elevated in both MSG and plasma from pSS patients with versus without ILD (p < 0.001). Furthermore, the CXCR2 expression level in MSG and plasma was significantly associated with the diffusing capacity of the lungs for carbon monoxide, erythrocyte sedimentation rate, and EULAR Sjögren’s Syndrome Disease Activity Index in ILD-pSS. Therefore, with its potential role in ILD progression in patients with pSS and its strong association with clinical manifestations of the disease, CXCR2 may serve as a useful index for disease activity in ILD associated with pSS.
Project description:Objective: The aim of this study was to characterize and compare the proteome in whole saliva, plasma, and salivary gland tissue in patients with primary Sjögren’s syndrome (pSS) and patients having symptoms of pSS, but not fulfilling the classification criteria, and to search for diagnostic biomarker candidates for pSS. Methods: Liquid chromatography tandem mass spectrometry was conducted on whole saliva, plasma, and labial salivary gland tissue samples from 24 patients with pSS and 16 non-Sjögren control subjects (non-pSS). Gene Ontology (GO)-terms and Kyoto Encyclopedia of Genes and Genomes (KEGG)-pathways were applied for functional annotation. Results: 1,013 proteins were identified in whole saliva, 219 in plasma, and 3,166 in salivary gland tissue. In saliva, 40 proteins differed significantly between the two groups. In pSS, proteins involved in immunoinflammatory processes were upregulated, whereas proteins related to salivary secretion were downregulated. The combination of neutrophil elastase, calreticulin, and tripartite motif-containing protein 29 yielded a receiver-operating characteristic (ROC) value of 0.97 (CI 0.93-1.00). Protein expression in plasma and salivary gland tissue did not differ between the patient groups. Conclusion: The salivary proteome of patients with pSS differed from that of non-pSS patients, indicating that saliva proteomics represents a promising non-invasive diagnostic tool for pSS.
Project description:Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by chronic inflammation of exocrine tissue, resulting in loss of tears and saliva. Patients also experience many extra-glandular disease manifestations. Treatment for pSS is palliative, and there are currently no treatments available that target disease etiology. Previous studies in our lab demonstrated that Myd88 is crucial for pSS pathogenesis in the NOD.B10Sn-H2b (NOD.B10) pSS mouse model, although the way in which Myd88-dependent pathways become activated in disease remains unknown. Based on its importance in other autoimmune diseases, we hypothesized that TLR7 activation accelerates pSS pathogenesis. We administered the TLR7 agonist Imiquimod (Imq) or sham treatment to pre-disease NOD.B10 females for 6 weeks. Parallel experiments were performed in age and sex-matched C57BL/10 controls. Imq-treated pSS animals exhibited cervical lymphadenopathy, splenomegaly, and expansion of TLR7-expressing B cells. Robust lymphocytic infiltration of exocrine tissues, kidney and lung was observed in pSS mice following treatment with Imq. TLR7 agonism also induced salivary hypofunction in pSS mice, which is a hallmark of disease. Anti-nuclear autoantibodies, including Ro (SSA) and La (SSB) were increased in pSS mice following Imq administration. Cervical lymph nodes from Imq-treated NOD.B10 animals demonstrated an increase in the percentage of activated/memory CD4+ T cells. Finally, aged-associated B cells (ABCs) were expanded in the spleens of Imq-treated pSS mice. Thus, activation of TLR7 accelerates local and systemic disease and promotes expansion of the ABC subset in pSS.
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.
Project description:Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the exocrine glands. Conventional dendritic cells (cDCs)-2 play a critical role in T and B cell activation, leading to germinal centre formation and autoantibody production. To understand the mechanisms underlying cDC2 dysregulation in pSS we performed RNA-sequencing analysis and functional validation on circulating cDC2s from pSS, non-Sjögren’s sicca (nSS) patients and healthy controls (HC). Two independent cohorts were established to identify reproducible dysregulated signatures, which included the interferon (IFN), toll-like receptors (TLR) signaling and antigen processing and presentation pathways. We confirm by flow cytometry that pSS-cDC2s were less efficient to degrade BSA but more efficient to uptake BSA both linked with the presence of anti-SSA antibodies. As the majority of the SSA+ pSS patients exhibit an IFN-signature, we tested whether IFNα priming would influence cDC2s antigen-uptake and processing. IFNα priming increased cDC2s uptake capacity, but not antigen processing. Additionally, pSS-cDC2s showed an increased uptake capacity of apoptotic salivary gland epithelial cells. Finally, pSS-cDC2s increased the proliferation of HC CD4+ T cells and the expression of CXCR3 and CXCR5 on the proliferating HC CD4+ T cells, contributing to T cell migration into the inflamed salivary glands. Here we provide the first in-depth molecular characterization of pSS-cDC2s and show that the transcriptomic and functional alterations observed in pSS-cDC2s are linked to IFN-signature. In view of its role in pSS immunopathology, delineating the molecular networks that drive cDC2s holds promise for targeting these cells in pSS.
Project description:Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by exocrine glands damage and extraglandular manifestations. To identify potential biomarkers for the early diagnosis of pSS and further investigate the potential mechanisms in progression of the disease, we combined our previous RNA- sequencing study and four microarrays data to conduct integrative transcriptome analyses in salivary glands (SGs) between the pSS and non-pSS. Differential gene expression analysis, gene co-expression network analysis and pathway analysis were conducted to detect hub gene, which was subsequently validated in peripheral blood. Correlation analysis, single-gene Gene Set Enrichment Analysis (GSEA) and receiver operating characteristic (ROC) curve were applied to investigate the role of ICOS in pSS and its classification capacity for pSS.
Project description:Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease characterized by abnormal immune cell activation. This study aimed to investigate differentially expressed long non-coding RNA (lncRNA) in peripheral blood mononuclear cells (PBMCs) in patients with pSS to identify lncRNAs that affect pSS pathogenesis. Transcriptome sequencing detected 38096 lncRNAs and 50869 mRNAs in PBMCs from patients with pSS and healthy individuals. The differentially expressed mRNAs underwent functional enrichment analysis. A protein interaction relationship (PPI) and ceRNA network was constructed. LncRNA expression in patients with pSS and controls was determined using RT-PCR. 1180 lncRNAs and 640 mRNAs were differentially expressed in pSS patients (fold change > 2 in healthy persons). The PPI network was constructed with 640 mRNAs and a ceRNA network with four key lncRNAs (GABPB1-AS1, PSMA3-AS1, LINC00847 and SNHG1). A co-expression relationship was found between GABPB1-AS1 and several upregulated mRNAs (IFI44, IFI44L, IFI6, and EPSTI1). RT-PCR revealed that GABPB1-AS1 and PSMA3-AS1 were significantly upregulated 3.0- and 1.4-fold in the pSS group, respectively. In patients with pSS, the GABPB1-AS1 expression level was positively correlated with B cell and IgG levels. GABPB1-AS1 expression levels are positively correlated with B cell levels and may be involved in the pathogenesis of pSS.
Project description:Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease with complex etiopathogenesis. Here we use Affymetrix U133 plus 2.0 microarray gene expression data from human parotid tissue. Parotid gland tissues were harvested from 17 pSS and 14 14 non-pSS sicca patients and 18 controls. The data were used in the following article: Nazmul-Hossain ANM, Pollard RPE, Kroese FGM, Vissink A, Kallenberg CGM, Spijkervet FKL, Bootsma H, Michie SA, Gorr SU, Peck AB, Cai C, Zhou H, Horvath S, Wong DTW (2012) Systems Analysis of Primary Sjögren’s Syndrome Pathogenesis in Salivary Glands: Comparative Pathways and Molecular Events in Humans and a Mouse Model. Parotid gland tissues were harvested from 17 pSS and 14 non-pSS sicca patients and 18 controls.