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Reumatologia Clinica May 2024Autoimmune diseases are known to be associated with an elevated risk of cardiovascular diseases; however, there exists a lack of awareness regarding this increased risk...
INTRODUCTION
Autoimmune diseases are known to be associated with an elevated risk of cardiovascular diseases; however, there exists a lack of awareness regarding this increased risk among patients.
OBJECTIVE
This study aimed to assess the prevalence of cardiovascular risk factors and events in various systemic autoimmune diseases, including Systemic Sclerosis (SSc), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjögren's syndrome (SS), matched by age, sex, and disease duration. Additionally, the study aimed to evaluate the perceived and actual risks of cardiovascular disease among patients.
METHODS
A cross-sectional self-reported survey on the patient's perspective of cardiovascular risk was conducted between January and June 2023. Sociodemographic and clinical data, including disease activity, were collected through medical records and questionnaires. Traditional cardiovascular risk factors and events were assessed, alongside the perceived cardiovascular risk. The SCORE calculation and Charlson Comorbidity Index (CCI) were employed for cardiovascular risk assessment.
RESULTS
Survey responses from 180 patients (45 patients each with SSc, SLE, RA, and SS) with systemic autoimmune diseases revealed that 20% perceived a low risk, 23% perceived neither lower nor higher, and 56% perceived a higher risk of developing cardiovascular diseases in the next ten years. Only 45% agreed that their autoimmune disease could increase the risk of a heart attack, even in the absence of other risk factors, and 46.7% were unaware that NSAIDs pose a cardiovascular risk. An association between cardiovascular risk measured by SCORE, comorbidities, and risk perception was observed in RA, SSc, and SS patients, with no association found in SLE patients (p=0.27). Except for SS patients (p=0.02), no association between CCI and disease activity level was found. Regarding the influence of age, working status, and education in CVD risk perception, an association between CVD risk perception and age was observed (p=0.01), with patients over 40 years exhibiting a higher perception of CVD risk. No differences were found regarding working status (p=0.19) nor education level (p=0.06).
CONCLUSIONS
Patients with SS, RA, and SSc displayed a heightened perception of cardiovascular risk, correlating with their actual risk and preexisting comorbidities. However, patients exhibited unawareness of certain cardiovascular risk behaviors. This underscores the need for tailored education programs on cardiovascular risk for autoimmune disease patients, to be implemented at the time of diagnosis and during follow-up in outpatient clinics.
Topics: Humans; Male; Female; Cross-Sectional Studies; Autoimmune Diseases; Cardiovascular Diseases; Middle Aged; Adult; Aged; Heart Disease Risk Factors; Self Report; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Scleroderma, Systemic; Risk Assessment; Prevalence; Self Concept; Risk Factors
PubMed: 38880551
DOI: 10.1016/j.reumae.2024.05.002 -
Archives of Biochemistry and Biophysics Jun 2024To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues...
To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-κB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-κB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-κB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-κB signaling by targeting IκBα, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.
PubMed: 38880321
DOI: 10.1016/j.abb.2024.110063 -
Biomedicine & Pharmacotherapy =... Jun 2024Sjögren's syndrome (SS) is an autoimmune disease in which the salivary glands (SGs) and the lacrimal glands (LGs) are affected by lymphocytic infiltration and...
Sjögren's syndrome (SS) is an autoimmune disease in which the salivary glands (SGs) and the lacrimal glands (LGs) are affected by lymphocytic infiltration and inflammation. It has been reported that interferon-α (IFN-α) released by plasmacytoid dendritic cells (pDCs) contribute to the pathology of SS, and ART has been shown to effectively ameliorates SS. Despite the current research endeavors, the mechanism of how ART works in the treatment of SS remains to be fully elucidated. Whether ART can treat SS by inhibiting IFN-α remains unclear. This hypothesis was tested both in vivo and in vitro settings during the study. The SS model mice, which were treated with ART, showed amelioration in symptoms related to dryness. RNA-seq analysis revealed strong anti-IFN-α signaling response upon ART treatment. Additional in vitro studies provided further confirmation that the application of ART inhibits the MyD88 protein expression and the nuclear translocation of IRF7. This suggests that the intervention of ART in the TLR-MyD88-IRF7 pathway plays a role in the therapeutic approach for SS. In summary, this study highlighted the therapeutic potential of ART in SS and ART inhibited the IFN-α signaling in pDCs via the TLR-MyD88-IRF7 pathway.
PubMed: 38878633
DOI: 10.1016/j.biopha.2024.116885 -
Gene Jun 2024Keratoconjunctivitis sicca (KCS) is an ocular condition characterized by insufficient tear production and inflammatory irritation, with Sjögren's syndrome (SS) being a...
Keratoconjunctivitis sicca (KCS) is an ocular condition characterized by insufficient tear production and inflammatory irritation, with Sjögren's syndrome (SS) being a major causative factor. This study aimed to extract patient transcriptomic data from the GEO database to identify signature genes associated with the diagnosis and treatment of KCS and the expression of three key genes were experimentally verified. We performed a difference analysis on the SS patient dataset and performed a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the resulting genes. Additionally, a Weighted Gene Co-expression Network Analysis (WGCNA) was constructed. Machine learning techniques were employed to analyze the most strongly correlated gene modules with SS traits. These findings were further validated using KCS immune-correlation microarrays as a validation set. The correlation of the three identified genes with 22 immune cells was assessed through immune infiltration analysis. Subsequently, a rat model of desiccated keratoconjunctivitis was established, and the modeling situation and expression of characteristic genes were analyzed at the morphological, tissue, and molecular levels. Bioinformatic prediction revealed that the expression of JAK1, SKI, ZBTB16 not only differed in the machine learning validation set, but also correlated with some immune cells in the immune infiltration analysis. The results of animal experiments showed that the transcription and expression levels of these three genes were significantly different in rat KCS tissues and normal tissues, and there were also differences in the expression of JAK1 and SKI in rat peripheral blood, as well as significant up-regulation of the expression of related inflammatory factors in KCS tissues. Through bioinformatics prediction and animal experimental validation, this study identified three differentially expressed genes in SS mediated KCS patients, which provide new potential biological targets for the diagnosis and treatment of KCS.
PubMed: 38876403
DOI: 10.1016/j.gene.2024.148691 -
Medicine Jun 2024This study employs CiteSpace software to analyze the research status, hotspots, and trends of primary Sjogren syndrome (pSS). Relevant publications from 1999 to 2023...
This study employs CiteSpace software to analyze the research status, hotspots, and trends of primary Sjogren syndrome (pSS). Relevant publications from 1999 to 2023 were searched in the Web of Science Core Collection (WoSCC) set, followed by generating a network map using CiteSpace software to identify top authors, institutions, countries, keywords, journals, references, and research trends. A total of 3564 valid articles were included in this study. The People Republic of China had the highest number of articles (n = 524), while the University of Bergen emerged as the institution with the highest publication count (n = 94). Mariette X was identified as the author with the most publications (n = 67), whereas Vitali C received recognition as the most cited author (n = 1706). Annals of Rheumatic Diseases stood out as the journal with the highest citation count (n = 2530). Notably, an article published in the Annals of Rheumatic Diseases in 2017 garnered significant attention by being cited a remarkable 304 times. The bibliometric analysis reveals that key areas of research in pSS encompass investigating pathogenesis; advancing and applying targeted biological agents; and establishing treatment and diagnostic standards.
Topics: Sjogren's Syndrome; Bibliometrics; Humans; Software
PubMed: 38875384
DOI: 10.1097/MD.0000000000038162 -
International Journal of Rheumatic... Jun 2024
Topics: Humans; Sjogren's Syndrome; Granuloma; Female; Dermatitis; Neutrophils; Treatment Outcome; Biopsy; Skin; Middle Aged
PubMed: 38874357
DOI: 10.1111/1756-185X.15228 -
Clinical Rheumatology Jun 2024Circular RNAs (circRNAs) play various roles in the development of many autoimmune diseases. However, their expression profiles and specific function in Sjögren's...
BACKGROUND
Circular RNAs (circRNAs) play various roles in the development of many autoimmune diseases. However, their expression profiles and specific function in Sjögren's Syndrome remains largely unknown.
OBJECTIVES
We aimed to investigate circRNAs potential diagnostic value in primary Sjögren's syndrome (pSS) and contribution to the pathogenesis of pSS.
METHODS
This study included 102 subjects, 51 pSS patients and 51 healthy controls. The concentration of hsa_circ_0045800 was analyzed in peripheral blood mononuclear cells obtained from 51 pSS patients and 51 healthy controls by qRT-PCR. We established a receiver operating characteristic curve (ROC) to assess the biological diagnostic value of hsa_circ_0045800 for pSS. In addition, we analyzed the correlation between hsa_circ_0045800 and disease activity in Sjogren's syndrome. A differential analysis was also conducted on the concentration of hsa_circ_0045800 in patients in pSS patients before and after treatment. We studied the downstream mechanism of hsa_circ_0045800 through bioinformatics analysis and confirmed it using luciferase reporter gene assay.
RESULTS
We confirmed that the concentration of hsa_circ_0045800 was elevated 10.4-fold in peripheral blood mononuclear cells of pSS patients than in healthy controls (p = 0.00). In the pSS active disease group, the concentration of hsa_circ_0045800 is 2.5-fold higher compared to the pSS non-active disease group (p = 0.04). The concentration of hsa_circ_0045800 after treatment was decreased by 80% compared with that before treatment (p = 0.037), suggesting its utility as a potential marker for monitoring treatment efficacy. ROC curve analysis showed that the diagnostic value of hsa_circ_0045800 in pSS patients was significantly higher than that in healthy controls, with an area under the curve of 0.865, a sensitivity of 74%, and a specificity of 92%. The concentration of hsa_circ_0045800 is correlated with various clinical factors: the concentration of hsa_circ_0045800 is positively associated with age (r = 0.328, P = 0.019), oral dryness (r = 0.331, P = 0.017), while it is negatively correlated with HGB (r = -0.435, P = 0.001) and and hypothyroidism (r = -0.318, P = 0.023). Bioinformatics predictions and luciferase assays indicated that hsa_circ_0045800 acts as a molecular sponge for miR-1247-5p, with SMAD2 being a target gene of miR-1247-5p.
CONCLUSION
Our study results show that hsa_circ_0045800 potentially contributes to the development and progression of pSS via the miR-1247-5p/SMAD2 pathway. Peripheral blood mononuclear cells are directly involved in the pathogenesis of pSS, and the discovery of hsa_circ_0045800 in peripheral blood mononuclear cells highlights its potential as a novel biomarker for disease activity and diagnosis in patients with pSS. Key Points • The concentration of hsa_circ_0045800 was higher in peripheral blood mononuclear cells of pSS patients. • Hsa_circ_0045800 promoted pSS progression through miR-1247-5p-SMAD2 axis. • Hsa_circ_0045800 is a potential biomarker for pSS.
PubMed: 38866992
DOI: 10.1007/s10067-024-06999-0 -
Frontiers in Immunology 2024The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between...
BACKGROUND
The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated.
METHODS
Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren's syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn's disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships.
RESULTS
There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings.
CONCLUSIONS
There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.
Topics: Humans; T-Lymphocytes, Regulatory; Genome-Wide Association Study; Mendelian Randomization Analysis; Risk Factors; Autoimmune Diseases; Lymphoma, Non-Hodgkin; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38863695
DOI: 10.3389/fimmu.2024.1374938 -
Zhonghua Jie He He Hu Xi Za Zhi =... Jun 2024To analyze of the clinical, imaging, and pathological features of pulmonary light chain deposition disease(PLCDD) secondary to Sjögren's syndrome(SS), and to improve...
To analyze of the clinical, imaging, and pathological features of pulmonary light chain deposition disease(PLCDD) secondary to Sjögren's syndrome(SS), and to improve the understanding of the disease. We retrospectively analyzed the clinical data of 23 PLCDD cases diagnosed by pathology in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2009 to 2023, a total of 11 cases of PLCDD secondary to SS(SS-PLCDD) were selected, the median age was 51 years old(range:36~74),10 female and 1 male, the clinical, imaging, and pathological features were summarized. All 11 cases showed bilateral multiple pulmonary nodules on HRCT with 10 cases accompanied by cysts, 6 cases with vessels in the cystic wall or crossing the cysts. Microscopically, all 11 cases showed amorphous eosinophilic material with negative Congo red staining deposited in the lung, vascular involvement was common, with variable lymphocyte, plasma cell infiltration and multinucleated giant cell reaction, cysts formation was observed in 6 cases,1 case combined with pulmonary lymphoma. No extrapulmonary involvement in all 11 cases. Ten patients were treated with glucocorticoid and (or) immunosuppressants, 1 patient changed to bortezomib-dexamethasone chemotherapy after 1 year, with a mean follow-up of 50 months, 5 cases were stable on clinical and (or) HRCT findings, 2 cases showed remission on HRCT, 2 cases progressed on HRCT. SS-PLCDD affects predominantly middle-aged females with lesions confined to the lung; HRCT showed bilateral multiple nodules and thin-walled cysts. Pulmonary pathology presented as non-amyloid material with negative Congo red staining and interstitial changes associated with SS. The overall prognosis was good, but caution is advised regarding the underlying lymphoma.
Topics: Humans; Sjogren's Syndrome; Female; Middle Aged; Male; Retrospective Studies; Adult; Aged; Lung Diseases; Lung; Tomography, X-Ray Computed; Immunoglobulin Light Chains
PubMed: 38858203
DOI: 10.3760/cma.j.cn112147-20231013-00229 -
Primary biliary cholangitis and Sjogren's syndrome: bi-directional Mendelian randomization analysis.European Review For Medical and... May 2024Observational studies have shown a higher prevalence of Sjogren's syndrome (SjS) in patients with primary biliary cholangitis (PBC) than in the healthy population, but...
OBJECTIVE
Observational studies have shown a higher prevalence of Sjogren's syndrome (SjS) in patients with primary biliary cholangitis (PBC) than in the healthy population, but whether this correlation is causal needs further confirmation. This study aimed to investigate the bidirectional causal relationship between PBC and SjS using Mendelian randomization (MR) analysis.
MATERIALS AND METHODS
We used pooled data from a large-scale genome-wide association study (GWAS) to select mutually independent genetic loci associated with PBC and SjS in people of European ancestry as instrumental variables (IVs). The causal association between PBC and SjS was analyzed by MR analysis using inverse variance weighting (IVW) and weighted median methods, and the ratio of ratios (OR) was used as an evaluation index. In addition, sensitivity analyses, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and leave-one-out test, were performed to ensure the stability of the results.
RESULTS
A total of 20 validated IVs were selected for PBC, and the number of IVs for SjS was seven. Positive MR analysis showed that genetically predicted PBC was significantly associated with the risk of SjS (IVW OR=1.174, 95% CI: 1.107-1.246, p<0.001). The weighted median method further confirmed this result (OR=1.146, 95% CI: 1.053-1.247, p=0.016). Inverse MR analysis showed that genetic susceptibility to SjS also increased the risk of PBC (IVW OR=1.737, 95% CI: 1.280-2.357, p<0.001), and this result was also confirmed by the weighted median method (OR=1.398, 95% CI: 1.120-1.746, p=0.003).
CONCLUSIONS
Our study found that genetically predicted SjS increased the risk of PBC and vice versa in a European population. This may shed light on the etiology of PBC and the management of patients with SjS.
Topics: Humans; Mendelian Randomization Analysis; Sjogren's Syndrome; Liver Cirrhosis, Biliary; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38856131
DOI: 10.26355/eurrev_202405_36292