Genetics and epigenetics in primary Sjogren's syndrome.
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ABSTRACT:
SUBMITTER: Imgenberg-Kreuz J
PROVIDER: S-EPMC8121440 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The pathogenesis of Sjögren's syndrome has not been elucidated. There has been evidence that genetics play an important role in the development of this disease from earlier studies. However, till now only a number of genes have been identified to be associated with SS, and these have only a weak or moderate effect. In this review we summarize the findings of the genetics studies and emphasize the need of large multicenter projects that will increase the sample sizes to provide more meaningful associations, as is the case in other common autoimmune diseases.
| S-EPMC5660941 | biostudies-literature
Project description:The objective of the study was to identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjogren's syndrome (SS). METHODS: A 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. The results were validated by quantitative reverse transcriptase-polymerase chain reaction techniques. RESULTS: We found a distinct difference in gene expression levels in MSGs, enabling a simple class prediction method to correctly classify 19 of the 20 samples as either patient or control, based on the top 5 differentially expressed genes. The 50 most differentially expressed genes in the primary SS group compared with the control group were all up-regulated, and a clear pattern of genes involved in chronic inflammation was found. CXCL13 and CD3D were expressed in >/=90% of primary SS patients and in </=10% of the controls. Lymphotoxin beta, as well as a number of major histocompatibility complex genes, cytokines, and lymphocyte activation factors, manifested its role in the pathogenesis of SS. Numerous type I interferon genes related to virus infection were found among the top 200 genes, with increased expression in primary SS. Interestingly, the expression of carbonic anhydrase II, which is essential in saliva production and secretion, and the apoptosis regulator Bcl-2-like 2 were down-regulated in primary SS patients. CONCLUSION: We have identified distinct gene expression profiles in MSGs from patients with primary SS that provide new knowledge about groups of genes that are up-regulated or down-regulated during disease, constituting an excellent platform for forthcoming functional studies.
2013-11-14 | E-MTAB-2073 | biostudies-arrayexpress
Project description:Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by dysfunction and lymphocytic infiltration of the salivary and lacrimal glands. Besides the characteristic sicca complaints, pSS patients can present a spectrum of signs and symptoms, which challenges the diagnostic process. Various imaging techniques can be used to assist in the diagnostic work-up and follow-up of pSS patients. Developments in imaging techniques provide new opportunities and perspectives. In this descriptive review, we discuss imaging techniques that are used in pSS with a focus on the salivary glands. The emphasis is on the contribution of these techniques to the diagnosis of pSS, their potential in assessing disease activity and disease progression in pSS, and their contribution to diagnosing and staging of pSS-associated lymphomas. Imaging findings of the salivary glands will be linked to histopathological changes in the salivary glands of pSS patients.
| S-EPMC7463854 | biostudies-literature
Project description:Chromosome 22q11.2 deletion syndrome (22q11.2del) is a complex, multi-organ disorder noted for its varying severity and penetrance among those affected. The clinical problems comprise congenital malformations; cardiac problems including outflow tract defects, hypoplasia of the thymus, hypoparathyroidism, and/or dysmorphic facial features. Additional clinical issues that can appear over time are autoimmunity, renal insufficiency, developmental delay, malignancy and neurological manifestations such as schizophrenia. The majority of individuals with 22q11.2del have a 3 Mb deletion of DNA on chromosome 22, leading to a haploinsufficiency of ~106 genes, which comprise coding RNAs, noncoding RNAs, and pseudogenes. The consequent haploinsufficiency of many of the coding genes are well described, including the key roles of T-box Transcription Factor 1 (TBX1) and DiGeorge Critical Region 8 (DGCR8) in the clinical phenotypes. However, the haploinsufficiency of these genes alone cannot account for the tremendous variation in the severity and penetrance of the clinical complications among those affected. Recent RNA and DNA sequencing approaches are uncovering novel genetic and epigenetic differences among 22q11.2del patients that can influence disease severity. In this review, the role of coding and non-coding genes, including microRNAs (miRNA) and long noncoding RNAs (lncRNAs), will be discussed in relation to their bearing on 22q11.2del with an emphasis on TBX1.
| S-EPMC7016268 | biostudies-literature
Project description:Purpose of reviewTo determine the advances made in the genetics of systemic lupus erythematosus (SLE) or Sjögren's syndrome as the era of genome-wide association and high-throughput single nucleotide typing begins.Recent findingsSeveral genome-wide association studies have been performed in SLE but there are no such studies published or in progress for Sjögren's syndrome. Genetics and the functional significance of risk alleles in the interferon pathway are being worked out in detail. This is especially true for STAT4 and IRF5. Gene copy number variation, a major source of genetic variability, is important for several genes that impart risk for SLE. An X chromosome copy number dose effect has recently been identified. Genetic evaluation of Sjögren's syndrome is limited to small studies that have concentrated on genes already shown to be risk factors in SLE.SummaryKnowledge of the genetics of SLE is advancing rapidly, whereas that of Sjögren's syndrome lags behind considerably.
| S-EPMC8056840 | biostudies-literature
Project description:OBJECTIVE:To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. METHODS:We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. RESULTS:In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ?5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ?5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. CONCLUSION:The UKPSSR identified a number of options for trial design, including selection on ESSDAI ?5, ESSPRI ?5 and serological and other parameters.
| S-EPMC5854028 | biostudies-literature
Project description:ObjectiveTo determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjögren's syndrome (SS) patients and to compare them to healthy controls.MethodsData on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group.ResultsPrimary SS patients had a higher prevalence of hypertension (28–50% versus 15.5–25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it.ConclusionPrimary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.
| S-EPMC4529667 | biostudies-literature
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.
2023-10-24 | GSE236254 | GEO
Project description:10 saliva samples from patients with primary Sojgren's syndrome and 10 saliva samples from control subjects Keywords: Biomarker development
2007-12-31 | GSE7451 | GEO
Project description:Sjogren's syndrome (SjS) is a chronic autoimmune disorder characterized by immune cell infiltration and progressive injury to the salivary and lacrimal glands. As a consequence, patients with SjS develop xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes). SjS is the third most common rheumatic autoimmune disorder, affecting 4 million Americans with over 90% of patients being female. Current diagnostic criteria for SjS frequently utilize histological examinations of minor salivary glands for immune cell foci, serology for autoantibodies, and dry eye evaluation by corneal or conjunctival staining. SjS can be classified as primary or secondary SjS, depending on whether it occurs alone or in association with other systemic rheumatic conditions, respectively. Clinical manifestations typically become apparent when the disease is relatively advanced in SjS patients, which poses a challenge for early diagnosis and treatment of SjS. Therefore, SjS mouse models, because of their close resemblance to the human SjS, have been extremely valuable to identify early disease markers and to investigate underlying biological and immunological dysregulations. However, it is important to bear in mind that no single mouse model has duplicated all aspects of SjS pathogenesis and clinical features, mainly due to the multifactorial etiology of SjS that includes numerous susceptibility genes and environmental factors. As such, various mouse models have been developed in the field to try to recapitulate SjS. In this review, we focus on recent mouse models of primary SjS xerostomia and describe them under three categories of spontaneous, genetically engineered, and experimentally induced models. In addition, we discuss future perspectives highlighting pros and cons of utilizing mouse models and current demands for improved models.
| S-EPMC4425610 | biostudies-literature