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Ugeskrift For Laeger Aug 2021Sjögren's syndrome (SS) is a common autoimmune disease with a prevalence of 1%. SS affects primarily women between the age of 30 and 50 years. The classic... (Review)
Review
Sjögren's syndrome (SS) is a common autoimmune disease with a prevalence of 1%. SS affects primarily women between the age of 30 and 50 years. The classic manifestations are sicca symptoms, musculoskeletal pain and fatigue but the disease can affect all organs. SS is associated with the antibody anti-SSA antibodies. The patients have a 15-20 times higher risk of lymphoma and an increased risk of spontaneous abortion and AV-block in life-born children. In this review, we share the diagnostic process and risk stratification and outline the treatments available from private practice.
Topics: Adult; Child; Fatigue; Female; Humans; Middle Aged; Prevalence; Sjogren's Syndrome
PubMed: 34378522
DOI: No ID Found -
Journal of Clinical Laboratory Analysis Feb 2021Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients...
BACKGROUND
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups.
METHODS
Ninety-nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K-mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal-Wallis test and the Bonferroni test.
RESULTS
Higher IFN-γ, IL-17F, IL-21, IL-23, IL-4, and IL-31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity.
CONCLUSION
Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.
Topics: Adult; Aged; Case-Control Studies; Cytokines; Female; Humans; Male; Middle Aged; Principal Component Analysis; Severity of Illness Index; Sjogren's Syndrome
PubMed: 33070375
DOI: 10.1002/jcla.23629 -
Annals of the Rheumatic Diseases Jun 2010To develop a disease activity index for patients with primary Sjögren's syndrome (SS): the European League Against Rheumatism (EULAR) Sjögren's syndrome disease...
OBJECTIVE
To develop a disease activity index for patients with primary Sjögren's syndrome (SS): the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI).
METHODS
Thirty-nine SS experts participated in an international collaboration, promoted by EULAR, to develop the ESSDAI. Experts identified 12 organ-specific 'domains' contributing to disease activity. For each domain, features of disease activity were classified in three or four levels according to their severity. Data abstracted from 96 patients with systemic complications of primary SS were used to generate 702 realistic vignettes for which all possible systemic complications were represented. Using the 0-10 physician global assessment (PhGA) scale, each expert scored the disease activity of five patient profiles and 20 realistic vignettes. Multiple regression modelling, with PhGA used as the dependent variable, was used to estimate the weight of each domain.
RESULTS
All 12 domains were significantly associated with disease activity in the multivariate model, domain weights ranged from 1 to 6. The ESSDAI scores varied from 2 to 47 and were significantly correlated with PhGA for both real patient profiles and realistic vignettes (r=0.61 and r=0.58, respectively, p<0.001). Compared with 57 (59.4%) of the real patient profiles, 468 (66.7%) of the realistic vignettes were considered likely or very likely to be true.
CONCLUSIONS
The ESSDAI is a clinical index designed to measure disease activity in patients with primary SS. Once validated, such a standardised evaluation of primary SS should facilitate clinical research and be helpful as an outcome measure in clinical trials.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Observer Variation; Reproducibility of Results; Severity of Illness Index; Sjogren's Syndrome
PubMed: 19561361
DOI: 10.1136/ard.2009.110619 -
Journal of Neurology Jun 2023Neurological manifestations of Sjögren's syndrome can be severe but also treatment-responsive. We aimed to systematically evaluate neurological manifestations of...
OBJECTIVE
Neurological manifestations of Sjögren's syndrome can be severe but also treatment-responsive. We aimed to systematically evaluate neurological manifestations of primary Sjögren's syndrome and find clinical features allowing sufficient identification of affected patients (pSSN) among those with Sjögren's syndrome without neurological involvement (pSS).
METHODS
Para-/clinical features of patients with primary Sjögren's syndrome (2016 ACR/EULAR classification criteria) were compared between pSSN and pSS. At our university-based center, patients with suggestive neurological symptoms undergo screening for Sjögren's syndrome, and newly diagnosed pSS patients are thoroughly evaluated for neurologic involvement. pSSN disease activity was rated by the Neurological Involvement of Sjögren's Syndrome Disease Activity Score (NISSDAI).
RESULTS
512 patients treated for pSS/pSSN at our site between 04/2018 and 07/2022 were included (238 pSSN patients [46%] vs. 274 pSS patients [54%], cross-sectional design). Independent predictors of neurological involvement in Sjögren's syndrome were male sex [p < 0.001], older age at disease onset [p < 0.0001], hospitalization at first presentation [p < 0.001], lower IgG levels [p = 0.04] and higher eosinophil values (treatment-naïve) [p = 0.02]. Univariate regression additionally showed older age at diagnosis [p < 0.001], lower prevalence of rheumatoid factor [p = 0.001], SSA(Ro)/SSB(La) antibodies [p = 0.03; p < 0.001], higher white blood cell count [p = 0.02] and CK levels [p = 0.02] (treatment-naïve) in pSSN.
INTERPRETATION
Patients with pSSN had different clinical characteristics than patients with pSS and represented a large proportion of the cohort. Our data suggest that neurological involvement in Sjögren's syndrome has been underestimated. Intensified screening for neurologic involvement should be included in the diagnostic algorithm for Sjögren's syndrome, especially in males of older age and with severe disease course requiring hospitalization.
Topics: Humans; Male; Female; Sjogren's Syndrome; Cross-Sectional Studies; Prevalence; Disease Progression
PubMed: 36802030
DOI: 10.1007/s00415-023-11613-5 -
Arthritis Research & Therapy Feb 2024Sjögren's disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic... (Review)
Review
Sjögren's disease is a heterogeneous autoimmune disorder that may be associated with systemic manifestations such as pulmonary or articular involvement. Systemic complications have prognostic implications and need to be identified and managed in a timely manner. Treatment should be tailored to the type and severity of organ involvement, ideally based on multidisciplinary evaluation.
Topics: Humans; Sjogren's Syndrome; Autoimmune Diseases
PubMed: 38331820
DOI: 10.1186/s13075-024-03262-4 -
International Journal of Molecular... Aug 2023Primary Sjögren's syndrome (pSS) is a connective tissue disease characterized by a wide spectrum of clinical features, extending from a benign glandular disease to an... (Review)
Review
Primary Sjögren's syndrome (pSS) is a connective tissue disease characterized by a wide spectrum of clinical features, extending from a benign glandular disease to an aggressive systemic disorder and/or lymphoma. The pathogenesis of Sjögren's syndrome (SS) is not completely understood, but it is assumed that pathogenesis of SS is multifactorial. The studies based on the animal models of SS provided significant insight in SS disease pathogenesis and management. The aim of this review is to summarize current studies on animal models with primary SS-like symptoms and discuss the impact of these studies on better understanding pathogenesis and management of Sjögren's syndrome. Databases PubMed, Web of Science, Scopus and Cochrane library were searched for summarizing studies on animal models in SS. Available data demonstrate that animal models are highly important for our understanding of SS disease.
Topics: Animals; Sjogren's Syndrome; Models, Animal; Aggression; Databases, Factual; Gene Library
PubMed: 37629175
DOI: 10.3390/ijms241612995 -
International Journal of Molecular... Nov 2020Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the... (Review)
Review
Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-β) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-β superfamily members, TGF-β1 and 2 are pro-fibrotic ligands, whereas TGF-β3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-β1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjögren's syndrome. Potential therapeutic strategies that target multiple levels in the TGF-β pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-β signaling in salivary gland fibrosis and advances of potential therapeutic options in the field.
Topics: Animals; Disease Susceptibility; Fibrosis; Humans; Radiation; Salivary Glands; Signal Transduction; Sjogren's Syndrome; Transforming Growth Factor beta
PubMed: 33266300
DOI: 10.3390/ijms21239138 -
QJM : Monthly Journal of the... Dec 2012Symptoms in keeping with autonomic dysfunction are commonly described by primary Sjögrens syndrome patients (pSS); whether objective abnormalities of autonomic function...
BACKGROUND
Symptoms in keeping with autonomic dysfunction are commonly described by primary Sjögrens syndrome patients (pSS); whether objective abnormalities of autonomic function occur is unclear. This study set out to explore dynamic cardiovascular autonomic responses in pSS and their relationship with symptoms and quality of life.
METHODS
Twenty-one people from the UK pSS registry, 21 community controls and 21 patients with the autoimmune liver disease primary biliary cirrhosis (PBC) (matched case-wise for age and sex) attended for assessment of autonomic responses to orthostasis and Valsalva manoeuvre (VM). pSS patients also completed EULAR Sjögrens Syndrome patient-reported index (ESSPRI), EULAR Sjögren's syndrome disease activity index (ESSDAI), fatigue impact scale and EURO-QOL 5-dimension (EQ-5D).
RESULTS
Compared with controls, pSS patients had significantly lower baseline systolic blood pressure (SBP) (114 ± 13 vs. 127 ± 20; P = 0.02), which dropped to a significantly lower value (98 ± 22 vs. 119 ± 24, P = 0.009). When area under the curve (AUC) was calculated for when the SBP was below baseline this was significantly greater in pSS compared to both control groups (pSS vs. control vs. PBC: 153 ± 236 vs. 92 ± 85 vs. 1.2 ± 0.3, P = 0.005). Peak phase IV SBP during the VM was significantly lower in pSS (P = 0.007) indicating early sympathetic failure. Increased heart rate associated with fatigue (P = 0.02; r(2) = 0.2) and EQ-5D. A shift in sympathetic-vagal balance associated with overall symptom burden (ESSPRI) (P = 0.04, r(2) = 0.3) and EULAR sicca score (P = 0.016; r(2) = 0.3), the latter also correlated with baroreceptor effectiveness (P = 0.03; r(2) = 0.2) and diastolic blood pressure variability (P = 0.003; r(2) = 0.4).
CONCLUSION
pSS patients have impaired blood pressure response to standing. Dysautonomia correlates with PSS-associated symptoms and quality of life.
Topics: Adult; Aged; Area Under Curve; Autonomic Nervous System; Blood Pressure; Case-Control Studies; Dizziness; Fatigue; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Quality of Life; Sjogren's Syndrome; Valsalva Maneuver
PubMed: 22976617
DOI: 10.1093/qjmed/hcs172 -
Arthritis Research & Therapy 2011Treatment of Sjögren's syndrome is almost entirely symptomatic. A lack of true understanding of the underlying immunological pathology of the disease prevents directed...
Treatment of Sjögren's syndrome is almost entirely symptomatic. A lack of true understanding of the underlying immunological pathology of the disease prevents directed therapy. Interleukin-21 (IL-21) is elevated in the serum of patients with this disease and is expressed by the lymphocytes infiltrating the salivary glands. The known functions of IL-21 in facilitating differentiation, proliferation, and survival of both B and T cells mesh well with the findings in Sjögren's syndrome. Demonstration of IL-21 as a fundamental aspect of the pathophysiology of Sjögren's syndrome could lead to the development of anti-IL-21 therapy for this disease.
Topics: Female; Gene Expression Regulation; Humans; Interleukins; Male; Salivary Glands; Sjogren's Syndrome
PubMed: 22226370
DOI: 10.1186/ar3518 -
Scientific Reports Dec 2021Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The...
Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.
Topics: Autoantibodies; DNA Methylation; Epigenomics; Female; Gene Expression; Gene Expression Regulation; Genetic Variation; HLA Antigens; Humans; Interferons; Male; Sjogren's Syndrome
PubMed: 34857786
DOI: 10.1038/s41598-021-01324-0