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Inflammopharmacology Feb 2024Sjögren's syndrome (SS) is characterised as keratoconjunctivitis sicca (dry eyes), xerostomia (dry mouth) commonly associated with salivary gland enlargement, and is...
Sjögren's syndrome (SS) is characterised as keratoconjunctivitis sicca (dry eyes), xerostomia (dry mouth) commonly associated with salivary gland enlargement, and is referred to as Primary Sjögren's syndrome. It is known as Secondary Sjögren's syndrome when it occurs in patients, with connective tissue disease, such as rheumatoid arthritis, systemic lupus erythematosus, polyarthritis nodosa, polymyositis, and systemic sclerosis. SS has also been associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation, human immunodeficiency syndrome (AIDS), hepatitis C infection (HCV), chronic biliary cirrhosis, neoplastic and myeloplastic syndromes, fibromyalgia, and chronic fatigue syndrome.
Topics: Humans; Sjogren's Syndrome; Arthritis, Rheumatoid; Fibromyalgia; Lupus Erythematosus, Systemic; Scleroderma, Systemic
PubMed: 37195497
DOI: 10.1007/s10787-023-01222-z -
Clinical and Experimental Rheumatology Dec 2023Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterised by the T-cell-mediated hyperactivation of B-cells and cytokine production. The... (Review)
Review
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterised by the T-cell-mediated hyperactivation of B-cells and cytokine production. The condition may evolve from an asymptomatic, indolent course, with glandular involvement, to extra-glandular systemic manifestations up to lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T- and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. Recently, increasing research focused on the investigation of mechanisms underlying the complex pathogenesis of the disease and highlighted the multi-factorial nature of SS consisting of concomitant involvement of environmental, genetic, neuroendocrine and immune factors. In particular, many aspects have been investigated regarding genetic and epigenetics, the role of specific B- and T-cell phenotypes and the investigation of disease-specific biomarkers as predictors of disease development, activity, and lymphomagenesis. Surely, a deeper understanding of these multiple mechanisms may facilitate earlier diagnosis, enable subphenotyping of patients and open novel therapeutic possibilities to address the unmet needs of the disease in the upcoming years.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.
Topics: Humans; Sjogren's Syndrome; Salivary Glands; Salivary Glands, Minor; B-Lymphocytes; Lymphoma
PubMed: 38149515
DOI: 10.55563/clinexprheumatol/255qsx -
Clinica Chimica Acta; International... Aug 2023Saliva is a versatile biofluid that contains a wide variety of biomarkers reflecting both physiologic and pathophysiologic states. Saliva collection is noninvasive and... (Review)
Review
Saliva is a versatile biofluid that contains a wide variety of biomarkers reflecting both physiologic and pathophysiologic states. Saliva collection is noninvasive and highly applicable for tests requiring serial sampling. Furthermore, advances in test accuracy, sensitivity and precision for saliva has improved diagnostic performance as well as the identification of novel markers especially in oral disease processes. These include dental caries, periodontitis, oral squamous cell carcinoma (OSCC) and Sjögren's syndrome (SS). Numerous growth factors, enzymes, interleukins and cytokines have been identified and are the subject of much research investigation. This review highlights current procedures for successful determination of saliva biomarkers including preanalytical factors associated with sampling, storage and pretreatment as well as subsequent analysis. Moreover, it provides an overview of the diagnostic applications of these salivary biomarkers in common oral diseases.
Topics: Humans; Saliva; Mouth Neoplasms; Carcinoma, Squamous Cell; Dental Caries; Biomarkers; Sjogren's Syndrome; Biomarkers, Tumor
PubMed: 37536520
DOI: 10.1016/j.cca.2023.117503 -
Arthritis Research & Therapy Sep 2023Several observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear....
BACKGROUND
Several observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers.
METHODS
We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P < 0.0031 was considered significant, and P value between 0.0031 and 0.05 was considered to be suggestive of an association. Sensitivity analysis was performed to validate the causality. Moreover, additional analysis was used to assess the associations between SS and well-accepted risk factors of cancers.
RESULTS
After correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005-1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960-0.9985, P = 2.45 × 10) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158-0.9676, P = 1.65 × 10). Suggestive associations were found in liver and bile duct cancer (OR = 0.9999, 95% CI: 0.9997-1.0000, P = 0.0291) and cancer of urinary tract (OR = 0.9996, 95% CI: 0.9992-1.0000, P = 0.0281). No causal effect of SS on other cancer types was detected. Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. No evidence of the causal relationship was observed for cancers on SS.
CONCLUSIONS
SS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies.
Topics: Male; Female; Humans; Sjogren's Syndrome; Genome-Wide Association Study; Mendelian Randomization Analysis; Endometrial Neoplasms; Prostatic Neoplasms; Bile Duct Neoplasms; Urologic Neoplasms
PubMed: 37715206
DOI: 10.1186/s13075-023-03157-w -
Frontiers in Immunology 2023Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and...
Exploring the shared molecular mechanisms between systemic lupus erythematosus and primary Sjögren's syndrome based on integrated bioinformatics and single-cell RNA-seq analysis.
BACKGROUND
Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are common systemic autoimmune diseases that share a wide range of clinical manifestations and serological features. This study investigates genes, signaling pathways, and transcription factors (TFs) shared between SLE and pSS.
METHODS
Gene expression profiles of SLE and pSS were obtained from the Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify shared genes related to SLE and pSS. Overlapping genes were then subject to Gene Ontology (GO) and protein-protein interaction (PPI) network analyses. Cytoscape plugins cytoHubba and iRegulon were subsequently used to screen shared hub genes and predict TFs. In addition, gene set variation analysis (GSVA) and CIBERSORTx were used to calculate the correlations between hub genes and immune cells as well as related pathways. To confirm these results, hub genes and TFs were verified in microarray and single-cell RNA sequencing (scRNA-seq) datasets.
RESULTS
Following WGCNA and limma analysis, 152 shared genes were identified. These genes were involved in interferon (IFN) response and cytokine-mediated signaling pathway. Moreover, we screened six shared genes, namely and , out of which three genes, namely and were found to be highly expressed in both microarray and scRNA-seq datasets. IFN response and ITGB2 signaling pathway were identified as potentially relevant pathways. In addition, STAT1 and IRF7 were identified as common TFs in both diseases.
CONCLUSION
This study revealed and as the shared genes and identified STAT1 and IRF7 as the common TFs of SLE and pSS. Notably, the IFN response and ITGB2 signaling pathway played vital roles in both diseases. Our study revealed common pathogenetic characteristics of SLE and pSS. The particular roles of these pivotal genes and mutually overlapping pathways may provide a basis for further mechanistic research.
Topics: Humans; Single-Cell Gene Expression Analysis; Sjogren's Syndrome; Genes, Overlapping; Lupus Erythematosus, Systemic; CD18 Antigens; Computational Biology; Ubiquitin Thiolesterase
PubMed: 37614232
DOI: 10.3389/fimmu.2023.1212330 -
Arthritis & Rheumatology (Hoboken, N.J.) Feb 2024B cells are important in the pathogenesis of primary Sjögren's syndrome (pSS). Patients positive for Sjögren's syndrome antigen A/Sjögren syndrome antigen B (SSA/SSB)...
OBJECTIVE
B cells are important in the pathogenesis of primary Sjögren's syndrome (pSS). Patients positive for Sjögren's syndrome antigen A/Sjögren syndrome antigen B (SSA/SSB) autoantibodies are more prone to systemic disease manifestations and adverse outcomes. We aimed to determine the role of B cell composition, gene expression, and B cell receptor usage in pSS subgroups stratified for SSA/SSB antibodies.
METHODS
Over 230,000 B cells were isolated from peripheral blood of patients with pSS (n = 6 SSA-, n = 8 SSA+ single positive and n = 10 SSA/SSB+ double positive) and four healthy controls and processed for single-cell RNA sequencing (scRNA-seq) and single-cell variable, diversity, and joining (VDJ) gene sequencing (scVDJ-seq).
RESULTS
We show that SSA/SSB+ patients present the highest and lowest proportion of naïve and memory B cells, respectively, and the highest up-regulation of interferon-induced genes across all B cell subtypes. Differential usage of IGHV showed that IGHV1-69 and IGHV4-30-4 were more often used in all pSS subgroups compared with controls. Memory B cells from SSA/SSB+ patients displayed a higher proportion of cells with unmutated VDJ transcripts compared with other pSS patient groups and controls, indicating altered somatic hypermutation processes. Comparison with previous studies revealed heterogeneous clonotype pools, with little overlap in CDR3 sequences. Joint analysis using scRNA-seq and scVDJ-seq data allowed unsupervised stratification of patients with pSS and identified novel parameters that correlated to disease manifestations and antibody status.
CONCLUSION
We describe heterogeneity and molecular characteristics in B cells from patients with pSS, providing clues to intrinsic differences in B cells that affect the phenotype and outcome and allowing stratification of patients with pSS at improved resolution.
Topics: Humans; Sjogren's Syndrome; B-Lymphocytes; Autoantibodies; Phenotype
PubMed: 37610265
DOI: 10.1002/art.42683 -
Arquivos de Neuro-psiquiatria Dec 2023Sjogren's syndrome (SS) is a complex autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands, resulting in sicca symptoms.... (Review)
Review
Sjogren's syndrome (SS) is a complex autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands, resulting in sicca symptoms. Additionally, SS presents with neurological manifestations that significantly impact the nervous system. This review aims to provide a comprehensive overview of the neurological aspects of SSj, covering both the peripheral and central nervous system involvement, while emphasizing diagnosis, treatment, and prognosis.
Topics: Humans; Sjogren's Syndrome; Nervous System Diseases
PubMed: 38157875
DOI: 10.1055/s-0043-1777105 -
Inflammation Research : Official... Dec 2023The pathogenesis, diagnosis, and treatment of Sjögren's syndrome (SS) face many challenges, and there is an urgent need to develop new technologies to improve our... (Review)
Review
OBJECTIVE
The pathogenesis, diagnosis, and treatment of Sjögren's syndrome (SS) face many challenges, and there is an urgent need to develop new technologies to improve our understanding of SS.
METHODS
By searching the literature published domestically and internationally in the past 20 years, this artical reviewed the research of various omics techniques in SS.
RESULTS
Omics technology provided valuable insights into the pathogenesis, early diagnosis, condition and efficacy evaluation of SS. It is helpful to reveal the pathogenesis of the disease and explore new treatment schemes, which will open a new era for the study of SS.
CONCLUSION
At present, omics research has made some gratifying achievements, but there are still many uncertainties. Therefore, in the future, we should improve research techniques, standardize the collection of samples, and adopt a combination of multi-omics techniques to jointly study the pathogenesis of SS and provide new schemes for its treatment.
Topics: Humans; Sjogren's Syndrome; Multiomics
PubMed: 37878024
DOI: 10.1007/s00011-023-01797-x -
Medicina (Kaunas, Lithuania) Sep 2023Primary Sjögren's syndrome (pSS) is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin's lymphoma in... (Review)
Review
Primary Sjögren's syndrome (pSS) is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin's lymphoma in mucosa-associated lymphoid tissue. The pathogenesis of Sjögren's syndrome (SS) is not completely understood, but it is assumed that pathogenesis of SS is multifactorial. The microbiota plays a notable role in the development of autoimmune disorders, including Sjögren's syndrome. Molecular mimicry, metabolite changes and epithelial tolerance breakdown are pathways that might help to clarify the potential contribution of the microbiota to SS pathogenesis. This review aims to provide an overview of recent studies describing microbiota changes and microbiota mechanisms associated with Sjögren's syndrome. Data on the microbiota in SS from PubMed, Web of Science, Scopus and the Cochrane Library databases are summarized. Overall, the microbiota makes a major contribution to the development of Sjögren's syndrome and progression. Future microbiota studies should improve the management of this heterogeneous autoimmune disease.
Topics: Humans; Sjogren's Syndrome; Autoimmune Diseases; Databases, Factual; Microbiota
PubMed: 37763780
DOI: 10.3390/medicina59091661 -
Trends in Pharmacological Sciences Jul 2023Artificial intelligence (AI)-based predictive models are being used to foster a precision medicine approach to treat complex chronic diseases such as autoimmune and... (Review)
Review
Artificial intelligence (AI)-based predictive models are being used to foster a precision medicine approach to treat complex chronic diseases such as autoimmune and autoinflammatory disorders (AIIDs). In the past few years the first models of systemic lupus erythematosus (SLE), primary Sjögren syndrome (pSS), and rheumatoid arthritis (RA) have been produced by molecular profiling of patients using omic technologies and integrating the data with AI. These advances have confirmed a complex pathophysiology involving multiple proinflammatory pathways and also provide evidence for shared molecular dysregulation across different AIIDs. I discuss how models are used to stratify patients, assess causality in pathophysiology, design drug candidates in silico, and predict drug efficacy in virtual patients. By relating individual patient characteristics to the predicted properties of millions of drug candidates, these models can improve the management of AIIDs through more personalized treatments.
Topics: Humans; Sjogren's Syndrome; Artificial Intelligence; Autoimmune Diseases; Arthritis, Rheumatoid; Drug Development
PubMed: 37268540
DOI: 10.1016/j.tips.2023.04.005