2,497 results on '"Primary Sjögren's syndrome"'
Search Results
2. Open-Label Extension Study to Evaluate the Safety of Efgartigimod in Adult Patients With Primary Sjögren's Syndrome (Rho plus)
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Iqvia Pty Ltd
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- 2024
3. A Study of the Safety and Effectiveness of Efgartigimod in Patients With Primary Sjögren's Syndrome (pSS) (rho)
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Iqvia Pty Ltd
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- 2024
4. Screening, diagnosis, and monitoring of interstitial lung disease in autoimmune rheumatic diseases: A narrative review.
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Good, Samuel, Sparks, Jeffrey, and Volkmann, Elizabeth
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Inflammatory myositis ,Interstitial lung disease ,Primary Sjogren’s syndrome ,Rheumatoid arthritis ,Systemic lupus erythematosus ,Systemic sclerosis - Abstract
Interstitial lung disease (ILD) is a common and serious manifestation of autoimmune rheumatic diseases. While the prevalence of ILD differs among the individual autoimmune rheumatic diseases, ILD remains an important cause of morbidity and mortality in systemic sclerosis, systemic lupus erythematosus, mixed connective tissue disease, primary Sjögrens disease, rheumatoid arthritis, and idiopathic inflammatory myositis. The present review summarizes recent literature on autoimmune-associated ILD with a focus on screening and monitoring for ILD progression. Reflecting on the currently available evidence, the authors propose a guideline for monitoring for progression in patients with newly diagnosed autoimmune-associated ILD. This review also highlights clinical and biological predictors of progressive pulmonary fibrosis and describes opportunity for further study in the rapidly evolving area of rheumatology and pulmonology.
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- 2024
5. Efficacy and Safety of S95011 in Primary Sjögren's Syndrome Patients
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ADIR, a Servier Group company
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- 2024
6. Anti-BTLA Agonist Therapy in Subjects With Primary Sjogren's Syndrome
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Matthew C. Baker, Clinical Chief and Assistant Professor of Medicine
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- 2024
7. Autoreactive Anti-Ro/SSA IgE To Determine Primary SjögRen's Syndrome's Disease Activity (I GET DRY)
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Ministry of Health, France
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- 2024
8. Are ultrasonographic scoring systems of the salivary gland in primary Sjögren's syndrome suitable for examination of Type2 diabetes mellitus patients with sicca?
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Kahveci, Abdulvahap, Gümüştepe, Alper, Sunar, İsmihan, and Ataman, Şebnem
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STATISTICAL correlation , *DISEASE duration , *GLYCOSYLATED hemoglobin , *CLINICAL pathology , *TYPE 2 diabetes , *SUBMANDIBULAR gland , *RESEARCH , *SALIVARY glands , *SJOGREN'S syndrome , *PAROTID glands , *RHEUMATOLOGISTS - Abstract
Objective: This study aimed to compare the salivary gland ultrasonography(SGUS) findings in patients with primary Sjögren's Syndrome (pSS) and diabetes mellitus(DM) patients with sicca symptoms and to examine the relationship between salivary gland ultrasonography (SGUS) findings with clinical and laboratory parameters. Methods: In this study, 34 patients with pSS and 34 DM patients with sicca symptoms were included. In all patients, bilateral parotid, and submandibular gland ultrasonography (totally 272 glands) was performed by blinded rheumatologist, using the Hocevar and the Outcome Measures in Rheumatology (OMERACT) scoring system. Clinic and ultrasonographic variables were compared between groups. The association between SGUS score and disease duration was analyzed by correlation analysis. Results: Patients with pSS presented significantly higher SGUS scores than patients with DM (the Hocevar score; 20.93(± 9.65) vs. 3.82(± 3.71); p < 0.05, the OMERACT score; 5.96(± 2.30) vs. 2.07(± 1.65); p < 0.05, respectively). In patients with pSS, the submandibular gland scores were significantly higher than the parotid gland scores (right; p < 0.05 vs. left; p < 0.01) while DM patients showed significantly higher parotid gland scores (right; p < 0.05 vs. left; p < 0.05). In pSS patients, the SGUS scores were associated with disease duration (r = 0.57; r = 0.50; p < 0.05), symptom duration (r = 50; r = 0.47; p < 0.05), and the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index (ESSPRI)-dryness score (r = 0.35, r = 0.36; p < 0.05). However, in DM patients, the SGUS scores are highly correlated with the ESSPRI-dryness (r = 0.74, r = 0.72; p < 0.05) and HbA1C level (r = 0.91, r = 0.86; p < 0.05). Conclusions: This study demonstrated that major salivary gland involvement was more severe and correlated with disease duration, and submandibular gland was dominantly affected in pSS. Contrarily, in DM patients, salivary gland involvement was milder, parotid dominant and related to level of dryness and HbA1C, rather than disease duration when compared to pSS, [ABSTRACT FROM AUTHOR]
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- 2024
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9. Hypophysitis and central nervous system involvement in association with Sjögren's syndrome along with hypoparathyroidism: a case report.
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Yum, Jungyon, Lee, Sang-Won, Rhee, Yumie, and Heo, Kyoung
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SJOGREN'S syndrome , *AUTOIMMUNITY , *CENTRAL nervous system , *AUTOIMMUNE diseases , *TEMPORAL lobe , *HYPOPARATHYROIDISM , *XEROSTOMIA - Abstract
Background: Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms. Case presentation: We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms. Conclusion: This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Clinical Characteristics of Distinct Subgroups of Patients with Primary Sjögren's Syndrome Classified by Serological Profiles: A Comparison Study.
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Bodakçi, Erdal
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SJOGREN'S syndrome , *RAYNAUD'S disease , *AUTOIMMUNE thyroiditis , *RHEUMATOID factor , *TURKS - Abstract
Sjögren's syndrome (SS) is an autoimmune disease characterized by heterogeneous clinical presentation and the presence of various autoantibodies. This study aimed to determine the differences in clinical findings according to antibody positivity in patients with primary Sjögren syndrome (pSS) in the Turkish population. A retrospective study was conducted and 402 patients (378 women and 24 men) with pSS were analyzed. The patients were categorized into three subgroups based on serological tests. These were (1) quadruple seropositivity (positive for anti-Sjögren's syndrome-related antigen A antibodies (anti-SSA; anti-Ro) and anti-Sjögren's syndrome-related antigen B antibodies (anti-SSB; anti-La), rheumatoid factor (RF), and antinuclear antibody (ANA); (2) double seropositivity (positive for ANA and anti-SSA/Ro antibodies); and (3) quadruple seronegativity (negative for ANA, RF, anti-SSA/Ro and anti-SSB/La antibodies). The number of quadruple-seropositive patients was 72 (18.6%), double-seropositive 174 (43.2%), and quadruple-seronegative was 85 (21.1%). The age at diagnosis of quadruple-seropositive pSS was 42.4 ± 10.8, which was significantly younger than that of patients with double-seropositive and quadruple-seronegative pSS (p = 0.021, p = 0.112). In terms of organ involvement, salivary gland enlargement, arthralgia, arthritis, Raynaud's phenomenon, lymphadenopathy, cutaneous vasculitis, interstitial lung disease, neurological involvement, autoimmune thyroiditis, renal interstitial disease, anemia, leukopenia, hypergammaglobulinemia, and hypocomplementemia were more common in quadruple-seropositive patients with pSS than in quadruple-seronegative patients (p < 0.0001). The results of this study confirmed the strong impact of immunological markers on the pSS phenotype at the time of diagnosis. Immunological patterns play a central role in the phenotypic expression of the disease, even during the initial diagnostic phase, and can guide physicians in designing personalized treatment plans for patients with pSS. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Long‐term survival analysis of patients with primary Sjögren's syndrome in China: A multicenter retrospective cohort study.
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Yueting, Li, Lin, Qiao, Jian, Xu, Xinwang, Duan, Yongfu, Wang, Weiguo, Xiao, Xiaodan, Kong, Qin, Li, Songlou, Yin, Liyun, Zhang, Lijun, Wu, Chanyuan, Wu, Jiuliang, Zhao, Yanhong, Wang, Siyun, Chen, Dong, Xu, Mengtao, Li, Xiaofeng, Zeng, and Yan, Zhao
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SJOGREN'S syndrome , *PULMONARY arterial hypertension , *PROGNOSIS , *INTERSTITIAL lung diseases , *CAUSES of death - Abstract
Aim: This study aimed to evaluate the long‐term survival, causes of death, and prognostic factors in Chinese patients with primary Sjögren syndrome (pSS). Methods: We included patients with pSS registered in the Chinese Rheumatism Data Centre between May 2016 and December 2021, and collected baseline clinical, laboratory, and treatment data. Survival and standard mortality rates were calculated using general population mortality data. Factors related to mortality were identified using Cox proportional hazards regression. Results: Among the 8588 patients included, 274 died during a median follow‐up of 4.0 years. The overall standardized mortality ratio was 1.61 (95% CI: 1.43–1.81). Overall survival rates were 98.2% at 5 years and 93.8% at 10 years. The predominant causes of death were comorbidities, including cardiovascular diseases, tumors, and infections, while the most frequent pSS‐related causes of death were interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Male sex, older age, ILD, PAH, and high EULAR Sjögren's syndrome disease activity index (ESSDAI), thrombocytopenia, anemia, high immunoglobulin A (IgA) level, and glucocorticoid treatment independently increased the mortality risk, while using hydroxychloroquine was a protective factor. Conclusion: Mortality rates have significantly increased in Chinese patients with pSS. Comorbidities, rather than pSS‐related organ damage, were the main causes of death. All‐cause mortality was associated with male sex, older age, ILD, PAH, high ESSDAI, thrombocytopenia, anemia, high IgA level, and glucocorticoid treatment, whereas hydroxychloroquine use might improve the long‐term survival. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Risk of primary Sjogren's Syndrome following human papillomavirus infections: a nationwide population-based cohort study.
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Huang-Hsi Chen, Sheng-Kai Ma, Kevin, Chen Dong, Wen-Jung Chang, Kuan-Rong Gao, Wuu-Tsun Perng, Jing-Yang Huang, and Cheng-Chung Wei, James
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SJOGREN'S syndrome ,HUMAN papillomavirus ,VIRUS diseases ,PAPILLOMAVIRUS diseases ,INFECTION - Abstract
Introduction: Viral infection is an exogeneous factor for primary Sjogren's syndrome (pSS). This study investigated the association between human papillomavirus (HPV) infections and pSS through a nationwide population based cohort study. Methods: Patients with HPV infections between January, 1999 and December, 2013 were included. The incidence of new-onset pSS in patients with HPV infections and non-HPV controls were derived. The multiple Cox regression model derived the risk of pSS in patients with HPV infections. Subgroup analysis and sensitivity analysis were performed to validate the association. Results: During a follow-up period of 12 years, the adjusted hazard ratio (aHR) of pSS in patients with HPV infections was significantly higher than that in non-HPV controls (aHR=1.64, 95% CI=1.47-1.83, P<0.001). The risk of pSS increased with age and the risk increased by 2.64-fold (95% CI= 2.37-2.93) for those older than 45 years. The significant association between HPV infections and the risk of pSS persisted in the sensitivity analysis restricted in HPV infections that lasted over 12 months (aHR=1.63, 95%CI=1.45-1.83, P<0.0001). Subgroup analyses revealed that both male (aHR=1.83, 95%CI=1.47-2.28, P<0.0001) and female (aHR=1.58, 95%CI=1.40-1.79, P<0.0001) patients with HPV infections and HPVinfected patients aged between 16 and 45 years (aHR=1.60, 95%CI=1.34-1.91, P<0.0001) and over 45 years (aHR=1.67, 95%CI=1.46-1.91, P<0.0001) were associated with a significantly greater risk of pSS. Conclusion: Patients with HPV infections presented with a significantly higher risk of pSS, regardless of age and sex. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Interstitial Lung Disease Phenotypes and Predictive Risk Factors in Primary Sjögren's Syndrome.
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La Rocca, Gaetano, Ferro, Francesco, Sambataro, Gianluca, Elefante, Elena, Fulvio, Giovanni, Navarro, Inmaculada Concepción, Moretti, Michele, Romei, Chiara, Mosca, Marta, and Baldini, Chiara
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SJOGREN'S syndrome , *RAYNAUD'S disease , *INTERSTITIAL lung diseases , *RHEUMATOID factor , *UNIVARIATE analysis - Abstract
Background/Objectives: The prevalence of Interstitial Lung Disease (ILD) and risk factors for its development in patients with primary Sjögren's syndrome (pSS) are still debated, possibly due to the existence of heterogeneous pSS-related ILD phenotypes. The aims of this study were: 1. To investigate the prevalence and predictive factors for ILD development in a single-center pSS cohort; 2. To characterize different pSS-ILD phenotypes. Methods: Clinical, laboratory and imaging data of pSS patients attending our center from January 2019 to September 2023 were retrospectively analyzed. ILD presence was confirmed on HRCT. Results: Forty-three out of 474 enrolled pSS patients presented ILD (M:F = 6:37), accounting for an overall ILD prevalence of 9.1%. In 19 cases, ILD was the first manifestation of pSS (ILD-onset), while in 24 ILD was diagnosed after pSS (ILD-incident). Compared to ILD-onset, ILD-incident patients more often presented pSS-related hematologic abnormalities (p = 0.012), cutaneous involvement (p = 0.027), inflammatory arthralgias (p = 0.026), C4 hypocomplementemia (p = 0.012) and positive RF (p = 0.031). On the other hand, ILD-onset patients were significantly older at pSS diagnosis (p = 0.008) and presented more severe fibrosis on HRCT (p = 0.008). On the univariate analysis, higher ESSDAI (p = 0.011), Raynaud's phenomenon (p = 0.009), anti-Ro52 (p = 0.031), hypergammaglobulinemia (p = 0.011), Rheumatoid Factor (RF) (p = 0.038) and C4 hypocomplementemia (p = 0.044) at baseline were associated to ILD development during follow-up. On the multivariate analysis, the ESSDAI at baseline (p = 0.05) and Raynaud's phenomenon (p = 0.013) at baseline were the only independent predictors of ILD development. Conclusions: ILD is a relatively common and clinically heterogenous pSS manifestation. Elevated disease activity at pSS onset is a risk factor for ILD development, prompting careful follow-up and intriguingly suggesting that immunomodulatory therapies may prevent ILD. [ABSTRACT FROM AUTHOR]
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- 2024
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14. The circular RNA hsa_circ_0045800 serves as a favorable biomarker in pathogenesis of sjögren's syndrome.
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Zhu, Hong, Wang, Yi, Wang, Ge, Ling, Yitong, Tian, Jinhai, Zhou, Yan, Zhu, Rong, Wang, Rui, Wang, Ruixin, Zhang, Wenhui, and Zhang, Xiaoyu
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SJOGREN'S syndrome , *CIRCULAR RNA , *MONONUCLEAR leukocytes , *AUTOIMMUNE diseases , *RECEIVER operating characteristic curves , *BIOMARKERS - Abstract
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. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Causal relationship between multiple sclerosis and primary Sjögren's syndrome: a two-sample mendelian randomization study.
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Shen, Jie, Ye, Qiao, Luo, Fang, Yu, Tianhang, Miao, Jinli, Wang, Wenmin, and Yuan, Hui
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SJOGREN'S syndrome , *GENOME-wide association studies , *AUTOIMMUNE diseases , *GENETIC variation , *GENETIC disorders - Abstract
This study aims to investigate the causal relationship between primary Sjögren's syndrome (SS) and multiple sclerosis (MS) using a two-sample Mendelian randomization (MR) analysis to provide insights into their common mechanisms and implications for therapeutic strategies. We utilized data from Genome-Wide Association Studies (GWAS) for primary SS (1,290 cases and 213,145 controls) and MS (4,888 cases and 10,395 controls), restricted to European ancestry. Instrumental variables (IVs) were selected based on genetic variants associated with primary SS. The primary MR method was Inverse Variance Weighted (IVW), supplemented by MR Egger, Weighted Median, Simple Mode, and Weighted Mode algorithms to assess the bidirectional causal relationships between MS and primary SS. Sensitivity analyses, including MR-PRESSO and leave-one-out analysis, were conducted to ensure the robustness of our findings. After excluding SNPs with pleiotropic effects, 42 and 5 SNPs were identified as robust IVs for primary SS and MS, respectively. Our analysis revealed a significant protective effect of MS on primary SS, with IVW showing an OR of 0.896 (95% CI: 0.841–0.954, P = 0.001). No significant heterogeneity or horizontal pleiotropy was detected, supporting the reliability of the results. Our findings suggest a potential protective effect of MS against primary SS, indicating a negative causal association between these two autoimmune diseases. This adds valuable genetic evidence to the understanding of the complex interplay between primary SS and MS, offering new avenues for research and therapeutic interventions. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Ziwan-Taoren herb pair can exert an therapeutical effect in primary Sjogren's syndrome through inhibiting the TLR/NF-κB pathway.
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Kuok-Tong Lei, Yun-Xia Wu, Yun Lu, Zi-Shan Wang, Thi-Huong Nguyen, Qiu-Ying Cai, Wen Zhu, and Yue Wang
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SJOGREN'S syndrome , *TUMOR necrosis factors , *PATHOLOGICAL physiology , *SUBMANDIBULAR gland , *VASOACTIVE intestinal peptide , *FLAVONOLS - Abstract
Background: Ziwan and Taoren (ZT) is a classic medicine pair in the formula of Mai Dong Di Shao Decoction, has been used to treat primary Sjogren's syndrome (pSS) for more than 20 years. But its action mechanism is still unknown. This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS. Methods: Firstly, the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis. Secondly, the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques. Finally, efficacy and mechanism were conducted through in vivo experiments, such as water intake, spleen index, hematoxylin-eosin staining pathological changes, ELISA, Western Blot analysis, and immunofluorescence staining. Results: Nine active compounds were extracted from network pharmacology, including quercitrin, luteolin, kaempferol, β-sitosterol, isorhamnetin, galangin, hederagenin, diosmetin and gibberellin 7. Seven disease targets were identified: RELA, TP53, AKT1, interleukin (IL) 6, MAPK1, ESR1, IL10; with RELA being the most core target. KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process. preliminary results of molecular docking showed that ZT's active compounds bind well to the RELA (p65) receptor. In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice. The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased, while levels of inflammatory factors such as tumor necrosis factor-α, IL-6, and IL-1β along with protein expressions including toll-like receptor4, p-p65 and p-IKKα/β in NF-κB pathway were reduced. Conclusions: The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS, potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Are ultrasonographic scoring systems of the salivary gland in primary Sjögren’s syndrome suitable for examination of Type2 diabetes mellitus patients with sicca?
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Abdulvahap Kahveci, Alper Gümüştepe, İsmihan Sunar, and Şebnem Ataman
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Salivary gland ,Ultrasonography ,Primary Sjögren’s syndrome ,Inflammation ,Diabetes mellitus ,Sicca symptoms ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Abstract Objective This study aimed to compare the salivary gland ultrasonography(SGUS) findings in patients with primary Sjögren’s Syndrome (pSS) and diabetes mellitus(DM) patients with sicca symptoms and to examine the relationship between salivary gland ultrasonography (SGUS) findings with clinical and laboratory parameters. Methods In this study, 34 patients with pSS and 34 DM patients with sicca symptoms were included. In all patients, bilateral parotid, and submandibular gland ultrasonography (totally 272 glands) was performed by blinded rheumatologist, using the Hocevar and the Outcome Measures in Rheumatology (OMERACT) scoring system. Clinic and ultrasonographic variables were compared between groups. The association between SGUS score and disease duration was analyzed by correlation analysis. Results Patients with pSS presented significantly higher SGUS scores than patients with DM (the Hocevar score; 20.93(± 9.65) vs. 3.82(± 3.71); p
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- 2024
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18. Hypophysitis and central nervous system involvement in association with Sjögren’s syndrome along with hypoparathyroidism: a case report
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Jungyon Yum, Sang-Won Lee, Yumie Rhee, and Kyoung Heo
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Hypoparathyroidism ,Hypophysitis ,Primary Sjögren’s syndrome ,Polyautoimmunity ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms. Case presentation We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms. Conclusion This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs.
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- 2024
- Full Text
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19. Identification and Validation of IFI44 as a Novel Biomarker for Primary Sjögren’s Syndrome
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Wei B, Yue Q, Ka Y, Sun C, Zhao Y, Ning X, Jin Y, Gao J, Wu Y, and Liu W
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primary sjögren’s syndrome ,machine learning ,immune cell infiltration ,biomarker ,ifi44 ,Pathology ,RB1-214 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Bowen Wei,1,2,* Qingyun Yue,1,2,* Yuxiu Ka,1,2,* Chenyang Sun,1,2 Yuxing Zhao,1,2 Xiaomei Ning,1,2 Yue Jin,1,2 Jingyue Gao,1,2 Yuanhao Wu,1,2 Wei Liu1,2 1Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Liu, Email fengshiliuwei@163.comBackground: Primary Sjögren’s syndrome (pSS) is an autoimmune condition marked by lymphocyte infiltration in the exocrine glands. Our study aimed to identify a novel biomarker for pSS to improve its diagnosis and treatment.Methods: The gene expression profiles of pSS were obtained from the Gene Expression Omnibus (GEO) database. The specific differentially expressed genes (DEGs) were screened by the Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Recursive Feature Elimination with Support Vector Machines (SVM-RFE). A biomarker was picked out based on correlation and diagnostic performance, the connection between the biomarker and clinical traits and immune infiltrating cells was explored, and the biomarker’s protein expression level in the serum of pSS patients was detected by enzyme-linked immunosorbent assay (ELISA). The competitive endogenous RNA (ceRNA) network regulated by the biomarker was predicted to verify the reliability of the biomarker in diagnosing pSS.Results: IFI44, XAF1, GBP1, EIF2AK2, IFI27, and IFI6 showed prominent diagnostic ability, with the high accuracy (AUC = 0.859) and significance (R ≥ 0.8) of IFI44 within the training dataset. IFI44 strongly exhibited a negative correlation with resting NK cells, macrophages M0, and eosinophils, and a positive correlation with activated dendritic cells, naive B cells, and activated CD4 memory T cells. Furthermore, IFI44 was significantly positively correlated with clinical traits such as IgG, SSA, SSB, ANA, and ESSDAI, with its protein expression level in the serum of pSS patients being notably elevated compared to controls (p < 0.001). Finally, the ceRNA regulatory network showed that hsa-miR-944, hsa-miR-9-5p, hsa-miR-126-5p, and hsa-miR-335-3p were significantly targeted IFI44, suggesting that IFI44 may serve as a dependable biomarker for pSS.Conclusion: In this study, we dug out IFI44 as a biomarker for pSS, systematically studied the potential regulatory mechanism of IFI44, and verified its reliability as a biomarker for pSS.Keywords: primary Sjögren’s syndrome, machine learning, immune cell infiltration, biomarker, IFI44
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- 2024
20. Analysis of risk factors and development of a nomogram prediction model for renal tubular acidosis in primary Sjogren syndrome patients
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Yanzhen Zeng, Runzhi Liu, Shuyi Li, Jingwen Wei, Fei Luo, Yongkang Chen, and Dongmei Zhou
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Primary Sjögren’s syndrome ,Renal tubular acidosis ,Nomogram ,Risk factors ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Objective To investigate the risk factors of renal tubular acidosis (RTA) in patients with primary Sjögren’s syndrome (pSS) and create a personalized nomogram for predicting pSS-RTA patients. Method Data from 99 pSS patients who underwent inpatient treatment at our hospital from January 2012 to January 2024 were retrospectively collected and analyzed. Bootstrap resampling technique, single-factor, and multi-factor logistic regression analyses were used to explore the risk factors for pSS-RTA. A nomogram was developed based on the results of the multivariate logistic model. The model was evaluated through receiver operating characteristic curve, C-index, calibration curve, and decision curve analysis. In addition, we graded the severity of pSS-RTA patients and used univariate analysis to assess the relationship between pSS-RTA severity and risk factors. Results A multivariate logistic regression analysis revealed that concurrent thyroid disease, long symptom duration, subjective dry mouth, and positive RF were independent risk factors for pSS-RTA patients. Based on them, a personalized nomogram predictive model was established. With a p-value of 0.657 from the Hosmer-Lemeshow test, the model demonstrated a good fit. The AUC values in the training and validation groups were 0.912 and 0.896, indicating a strong discriminative power of the nomogram. The calibration curves for the training and validation groups closely followed the diagonal line with a slope of 1, confirming the model’s reliable predictive ability. Furthermore, the decision curve analysis showed that the nomogram model had a net benefit in predicting pSS-RTA, emphasizing its clinical value.This study did not find an association between the severity of pSS-RTA and risk factors. Discussion We developed a nomogram to predict RTA occurrence in pSS patients, and it is believed to provide a foundation for early identification and intervention for high-risk pSS patients.
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- 2024
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21. Study to Assess Safety and Effectiveness of Branebrutinib Treatment in Participants With Active Systemic Lupus Erythematosus or Primary Sjögren's Syndrome, or Branebrutinib Treatment Followed by Open-label Abatacept Treatment in Study Participants With Active Rheumatoid Arthritis
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- 2024
22. A Study to Evaluate the Efficacy and Safety of Telitacicept in Subjects With Active Primary Sjogren's Syndrome
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- 2023
23. Primary Sjögren’s syndrome: new perspectives on salivary gland epithelial cells
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Jiaqi Hou, Yiyi Feng, Zhixia Yang, Yimei Ding, Dandan Cheng, Zhonghao Shi, Rouxin Li, and Luan Xue
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Primary Sjögren’s syndrome ,Salivary gland epithelial cells ,Function ,Structure ,Pathogenesis ,Medicine - Abstract
Abstract Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease primarily affecting exocrine glands such as the salivary glands, leading to impaired secretion and sicca symptoms. As the mainstay of salivation, salivary gland epithelial cells (SGECs) have an important role in the pathology of pSS. Emerging evidence suggests that the interplay between immunological factors and SGECs may not be the initial trigger or the sole mechanism responsible for xerostomia in pSS, challenging conventional perceptions. To deepen our understanding, current research regarding SGECs in pSS was reviewed. Among the extensive aberrations in cellular architecture and function, this review highlighted certain alterations of SGECs that were identified to occur independently of or in absence of lymphocytic infiltration. In particular, some of these alterations may serve as upstream factors of immuno-inflammatory responses. These findings underscore the significance of introspecting the pathogenesis of pSS and developing interventions targeting SGECs in the early stages of the disease. Graphical Abstract
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- 2024
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24. The role of M1/M2 macrophage polarization in primary Sjogren’s syndrome
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Xiaochan Chen, Linjiang Zhu, and Huaxiang Wu
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Primary Sjogren’s syndrome ,Macrophage polarization ,Minor salivary gland ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background The purpose of this study was to investigate the role of macrophage polarization in the pathogenesis of primary Sjogren’s syndrome (pSS). Methods Peripheral venous blood samples were collected from 30 patients with pSS and 30 healthy controls. Minor salivary gland samples were abtainted from 10 of these patients and 10 non-pSS controls whose minor salivary gland didn’t fulfill the classification criteria for pSS. Enzyme-linked immuno sorbent assay was used to examine the serum concentration of M1/M2 macrophage related cytokines (TNF-a, IL-6, IL-23, IL-4, IL-10 and TGF-β). Flow cytometry was used to examine the numbers of CD86+ M1 macrophages and CD206+ M2 macrophages in peripheral blood mononuclear cells (PBMCs). Immunofluorescence was used to test the infiltration of macrophages in minor salivary glands. Results This study observed a significant increase in pSS patients both in the numbers of M1 macrophages in peripheral blood and serum levels of M1-related pro-inflammatory cytokines (IL-6, IL-23 and TNF-α). Conversely, M2 macrophages were downregulated in the peripheral blood of pSS patients. Similarly, in the minor salivary glands of pSS patients, the expression of M1 macrophages was increased, and that of M2 macrophages was decreased. Furthermore, a significantly positive correlation was found between the proportions of M1 macrophages in PBMCs and serum levels of IgG and RF. Conclusions This study reveals the presence of an significant imbalance in M1/M2 macrophages in pSS patients. The M1 polarization of macrophages may play an central role in the pathogenesis of pSS.
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- 2024
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25. Immunometabolic alteration of CD4+ T cells in the pathogenesis of primary Sjögren's syndrome.
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Chen, Yingying, Luo, Xuan, Deng, Chuiwen, Zhao, Lidan, Gao, Hui, Zhou, Jiaxin, Peng, Linyi, Yang, Huaxia, Li, Mengtao, Zhang, Wen, Zhao, Yan, and Fei, Yunyun
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SJOGREN'S syndrome , *T cells , *T cell differentiation , *T helper cells , *TH1 cells , *AUTOIMMUNE diseases - Abstract
Primary Sjögren's syndrome (pSS) is a prevalent autoimmune disorder wherein CD4+ T cells play a pivotal role in its pathogenesis. However, the underlying mechanisms driving the hyperactivity of CD4+ T cells in pSS remain poorly understood. This study aimed to investigate the potential role of immunometabolic alterations in driving the hyperactivity of CD4+ T cells in pSS. We employed Seahorse XF assay to evaluate the metabolic phenotype of CD4+ T cells, conducted flow cytometry to assess the effector function and differentiation of CD4+ T cells and measured the level of intracellular reactive oxygen species (ROS). Additionally, transcriptome sequencing, PCR, and Western blotting were utilized to examine the expression of glycolytic genes. Our investigation revealed that activated CD4+ T cells from pSS patients exhibited elevated aerobic glycolysis, rather than oxidative phosphorylation, resulting in excessive production of IFN-γ and IL-17A. Inhibition of glycolysis by 2-Deoxy-D-glucose reduced the expression of IFN-γ and IL-17A in activated CD4+ T cells and mitigated the differentiation of Th1 and Th17 cells. Furthermore, the expression of glycolytic genes, including CD3E, CD28, PIK3CA, AKT1, mTOR, MYC, LDHA, PFKL, PFKFB3, and PFKFB4, was upregulated in activated CD4+ T cells from pSS patients. Specifically, the expression and activity of LDHA were enhanced, contributing to an increased level of intracellular ROS. Targeting LDHA with FX-11 or inhibiting ROS with N-acetyl-cysteine had a similar effect on reversing the dysfunction of activated CD4+ T cells from pSS patients. Our study unveils heightened aerobic glycolysis in activated CD4+ T cells from pSS patients, and inhibition of glycolysis or its metabolite normalizes the dysfunction of activated CD4+ T cells. These findings suggest that aerobic glycolysis may be a promising therapeutic target for the treatment of pSS. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Primary Sjögren's syndrome: new perspectives on salivary gland epithelial cells.
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Hou, Jiaqi, Feng, Yiyi, Yang, Zhixia, Ding, Yimei, Cheng, Dandan, Shi, Zhonghao, Li, Rouxin, and Xue, Luan
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SJOGREN'S syndrome ,SALIVARY glands ,EPITHELIAL cells ,EXOCRINE glands ,AUTOIMMUNE diseases ,CELL physiology - Abstract
Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease primarily affecting exocrine glands such as the salivary glands, leading to impaired secretion and sicca symptoms. As the mainstay of salivation, salivary gland epithelial cells (SGECs) have an important role in the pathology of pSS. Emerging evidence suggests that the interplay between immunological factors and SGECs may not be the initial trigger or the sole mechanism responsible for xerostomia in pSS, challenging conventional perceptions. To deepen our understanding, current research regarding SGECs in pSS was reviewed. Among the extensive aberrations in cellular architecture and function, this review highlighted certain alterations of SGECs that were identified to occur independently of or in absence of lymphocytic infiltration. In particular, some of these alterations may serve as upstream factors of immuno-inflammatory responses. These findings underscore the significance of introspecting the pathogenesis of pSS and developing interventions targeting SGECs in the early stages of the disease. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Systematic review and meta-analysis of the diagnostic performance of lacrimal gland ultrasound elastography in primary Sjögren's syndrome.
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Zhang, Mingyan, Pan, Jianpeng, and Sheng, Junfa
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Objective: This research conducted a comprehensive evaluation of the effectiveness of ultrasonic elastography (USE) in detecting lacrimal gland involvement in individuals suffering from primary Sjögren's syndrome (pSS). Methods: A comprehensive search was undertaken across multiple databases including PubMed, the Cochrane Library, EMBASE, Wanfang, Web of Science, and the Chinese National Knowledge Infrastructure, to gather relevant literature pertaining to the application of USE in diagnosing pSS from January 1, 2000, to October 1, 2023. Pooled data were used to calculate sensitivity, specificity, and diagnostic odds ratios. Several summary metrics were used to evaluate SWE's performance in detecting pSS, including the area under the receiver operating characteristic curve, diagnostic odds ratios, sensitivities, and specificities. Results: Five pertinent studies included a total of 273 patients. Shear wave elastography (SWE) demonstrated a pooled sensitivity of 0.88 (95% CI 0.77–0.94) and specificity of 0.94 (95% CI 0.88–0.98), with an area under the receiver operating characteristic curve of 0.97 (95% CI 0.95–0.98). SWE exhibited a positive likelihood ratio of 15.86 (95% CI 6.99–36.00) and a negative likelihood ratio of 0.13 (95% CI 0.07–0.25). No evidence of publication bias was observed (p = 0.70). Conclusion: SWE demonstrates a remarkable degree of precision in detecting lacrimal gland involvement in individuals suffering from pSS. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Novel Therapeutic Approaches in Connective Tissue Disease-Associated Interstitial Lung Disease.
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Mulcaire-Jones, Erica, Pugashetti, Janelle Vu, Oldham, Justin M., and Khanna, Dinesh
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INTERSTITIAL lung diseases , *THERAPEUTICS , *CONNECTIVE tissue diseases , *CONNECTIVE tissues , *AUTOIMMUNE diseases , *SYSTEMIC scleroderma , *RHEUMATOID arthritis - Abstract
Connective tissue diseases (CTD) comprise a group of autoimmune diseases that can affect multiple organs in the body including the lungs. The most common form of pulmonary involvement is interstitial lung disease (ILD). CTD-associated ILD (CTD-ILD) can take one of several courses including nonprogressive, chronically progressive, or rapidly progressive. Chronically and rapidly progressive patterns are associated with increased mortality. Limited randomized controlled trial data are available for treatment of CTD-ILD, with most data coming from systemic sclerosis-related ILD. The current first-line treatment for all CTD-ILD is immunosuppression with consideration of antifibrotics, stem cell transplant, and lung transplant in progressive disease. In this article, we review data for ILD treatment options in systemic sclerosis, rheumatoid arthritis, myositis, and primary Sjögren's syndrome-related ILDs. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Pulmonary Hypertension in Connective Tissue Diseases Other than Systemic Sclerosis.
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Budhram, Brandon, Weatherald, Jason, and Humbert, Marc
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CONNECTIVE tissue diseases , *SYSTEMIC scleroderma , *EPIDEMIOLOGY , *SJOGREN'S syndrome , *PULMONARY arterial hypertension , *ENDOTHELIUM diseases , *PULMONARY hypertension - Abstract
Pulmonary hypertension (PH) is a known complication of certain connective tissue diseases (CTDs), with systemic sclerosis (SSc) being the most common in the Western world. However, PH in association with non-SSc CTD such as systemic lupus erythematous, mixed connective tissue disease, and primary Sjögren's syndrome constitutes a distinct subset of patients with inherently different epidemiologic profiles, pathophysiologic mechanisms, clinical features, therapeutic options, and prognostic implications. The purpose of this review is to inform a practical approach for clinicians evaluating patients with non-SSc CTD-associated PH. The development of PH in these patients involves a complex interplay between genetic factors, immune-mediated mechanisms, and endothelial cell dysfunction. Furthermore, the broad spectrum of CTD manifestations can contribute to the development of PH through various pathophysiologic mechanisms, including intrinsic pulmonary arteriolar vasculopathy (pulmonary arterial hypertension, Group 1 PH), left-heart disease (Group 2), chronic lung disease (Group 3), chronic pulmonary artery obstruction (Group 4), and unclear and/or multifactorial mechanisms (Group 5). The importance of diagnosing PH early in symptomatic patients with non-SSc CTD is highlighted, with a review of the relevant biomarkers, imaging, and diagnostic procedures required to establish a diagnosis. Therapeutic strategies for non-SSc PH associated with CTD are explored with an in-depth review of the medical, interventional, and surgical options available to these patients, emphasizing the CTD-specific considerations that guide treatment and aid in prognosis. By identifying gaps in the current literature, we offer insights into future research priorities that may prove valuable for patients with PH associated with non-SSc CTD. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Characteristics of the oral microbiota in patients with primary Sjögren's syndrome.
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Xie, Yiwen, Fan, Yu, Su, Miaotong, Wang, Yukai, and Zhang, Guohong
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SJOGREN'S syndrome , *ORAL microbiology , *DENTAL caries , *AUTOIMMUNE diseases , *RIBOSOMAL DNA , *MICROBIAL ecology , *HYPERVARIABLE regions , *NUCLEOTIDE sequencing - Abstract
Objective: Primary Sjögren's syndrome (pSS) is an autoimmune disease with unknown etiology that is considered to be related to environmental and genetic factors. The aim of this study was to clarify the oral microflora characteristics of pSS patients and to reveal the connection between oral bacterial composition and dental caries using a high-throughput sequencing technique. Methods: Thirty-five pSS patients and 20 healthy controls were enrolled in this study. We collected saliva and plaque samples from pSS patients and saliva samples from healthy controls. We used 16S ribosomal DNA (16S rDNA) high-throughput sequencing targeting the V3–V4 hypervariable region to determine the composition and structure of the microbiota in the three sample sets. Finally, bioinformatics analyses, including the diversity of the microbiota, species differences, and functional prediction were performed. Results: In the alpha diversity and beta diversity analysis, the Chao1 (P < 0.01), observed species (P < 0.01), and PD whole tree indices (P < 0.01) were significantly lower in the saliva and plaque samples of pSS patients than in the saliva samples of healthy controls, but the Shannon (P < 0.01) and Simpson indices (P < 0.01) were significantly higher in the healthy controls, and their total diversity significantly differed. In the main flora composition at the genus level (top 10), we identified Prevotella and Veillonella as more enriched in the saliva of pSS patients and Fusobacterium, Actinomyces, and Leptotrichia as more enriched in the plaque of pSS patients. Predictive functional analysis showed that the oral microbiota of pSS patients was related to translation, metabolism of cofactors and vitamins, and nucleotide metabolism. Conclusions: The oral microbial ecology of patients with pSS is dysregulated, resulting in a decrease in overall diversity. Prevotella and Veillonella may be related to pSS, while Fusobacterium, Actinomyces, and Leptotrichia may be related to dental caries in pSS patients. Key Points • This study revealed differences in the oral microbial composition of patients with pSS compared to healthy controls. • We included a plaque group of pSS patients to identify the microbiota related to pSS and dental caries. • Prevotella and Veillonella may contribute to pSS, and Fusobacterium, Actinomyces, and Leptotrichia are associated with dental caries in pSS patients. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Male patients with primary Sjögren's syndrome have unique clinical manifestations and circulating lymphocyte profiles.
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Liu, Huan, Yuan, Jiangshui, Tan, Xueying, Song, Weiqing, and Wang, Shuguo
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SJOGREN'S syndrome , *LYMPHOCYTE subsets , *LYMPHOCYTES , *SYMPTOMS , *PATIENTS - Abstract
Objectives: We aimed to explore the relationship between clinical characteristics and circulating lymphocyte profiles in Chinese male patients with primary Sjögren's syndrome (pSS). Method: Data from 397 patients with pSS were analyzed retrospectively. 37 were male, which is a prevalence of 9.3%. The clinical, laboratory, and immunophenotypic profiles of peripheral blood lymphocyte subsets were compared between male and female pSS patients. Results: Male patients with primary Sjögren's syndrome have unique clinical manifestations and circulating lymphocyte profiles. Male patients complained more about xerophthalmia and presented with more extra-glandular manifestations as compared with female patients. The CD4+/CD8+ ratio (P = 0.030), the prevalence of CD4−CD8− T cells in lymphocytes (P = 0.020), the absolute number of CD4−CD8− T cells (P = 0.035), the prevalence of CD4+ T cells in lymphocytes (P < 0.001), and the absolute number of CD4+ T cells (P = 0.023) were significantly lower in male patients compared to female patients. On the other hand, the prevalence of CD8+CD28+ T cells (P = 0.030) and CD4+CD25high T cells (P = 0.040) in lymphocytes was significantly higher in male patients than in female patients. Moreover, compared to females with pSS, an elevated serum IgG level, low C3 and C4 levels, anti-SSB positivity, and ANA titers of ≥ 1:160 positivity were more frequent in male with pSS. Conclusions: Male patients with pSS have distinctive peripheral blood lymphocyte subpopulations, present with more severe clinical symptoms and immunological features, and have an unfavorable prognosis. Key Points • Male patients with pSS have more severe clinical symptoms and specific characteristics of peripheral blood lymphocyte subsets. • Male pSS patients exhibit a higher intensity of the disease (as evaluated by ESSDAI). • Male patients with pSS require individualized treatment regimens and closer follow-up. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Emerging biologic frontiers for Sjogren's syndrome: Unveiling novel approaches with emphasis on extra glandular pathology.
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Xiao Xiao Li, Maierhaba Maitiyaer, Qing Tan, Wen Hui Huang, Yu Liu, Zhi Ping Liu, Yue Qiang Wen, Yu Zheng, Xing Chen, Rui Lin Chen, Yi Tao, and Shui Lian Yu
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SJOGREN'S syndrome ,PATHOLOGY ,BIOTHERAPY ,AUTOIMMUNE diseases ,EXOCRINE glands - Abstract
Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissueengineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Efficacy and safety of total glucosides of paeony in treating primary Sjögren's syndrome: a propensity-matched study.
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CUI, Y.-Y., ABDUKIYUM, M., XU, X.-F., ZHANG, Y.-Q., ZHAO, N., JIA, Z.-Y., ZHENG, Y.-Y., JIN, Z.-Y., HUANG, S.-S., and FENG, X.-B.
- Abstract
OBJECTIVE: This study aimed to evaluate the efficacy and safety of total glucosides of paeony (TGP) in patients with primary Sjögren's syndrome (pSS). PATIENTS AND METHODS: This study included 236 patients with pSS, including 118 TGP users and 118 non-users. Propensity score matching and Binary logistic regression analyses were used to minimize confounding factors and determine the association between TGP treatment and clinical variables. RESULTS: The baseline indexes of TGP users and non-users were basically the same. The median time of follow-up in the two groups was also similar (p < 0.05). Compared with non-users, TGP users showed higher rates of improvement in dry mouth and eyes and musculoskeletal involvement, as well as more significant reductions in serum alanine aminotransferase (ALT) and direct bilirubin (DBIL) levels after treatment. Logistic regression confirmed that the use of TGP was negatively correlated with the increase of ALT and DBIL in pSS patients, and the reduction in these variables was more pronounced after 2 years of treatment. The incidence of adverse reactions in the TGP users was 11.9%, which was compatible with those in non-users. CONCLUSIONS: TGP is often a safe option for treating pSS patients with musculoskeletal features and abnormal ALT levels. Besides, it can help improve dry mouth and dry eyes and decrease DBIL levels. [ABSTRACT FROM AUTHOR]
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- 2024
34. Melatonin improves salivary gland damage and hypofunction in pSS by inhibiting IL-6/STAT3 signaling through its receptor-dependent manner.
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Liu, Yi, Wang, Fang, Cheng, Bo, and Zhou, Gang
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SALIVARY glands , *SJOGREN'S syndrome , *DNA damage , *MELATONIN , *EXOCRINE glands - Abstract
Primary Sjogren's syndrome (pSS) is an autoimmune disease of the exocrine glands with no specific or efficient treatments. Melatonin, a natural hormone, is revealed to show multiple biological functions, both receptor-dependent and independent effects, including anti-apoptotic, antioxidant, and anti-inflammatory activities. However, the potential mechanism by which melatonin protects salivary glands (SGs) of pSS from damage needs to be clarified. The purpose of current study was to explore the role and receptor-related mechanisms of melatonin in pSS-induced glandular damage. NOD/Ltj mice were used to spontaneously mimic pSS-induced glandular hypofunction in vivo and primary human salivary gland epithelial (HSGE) cells were stimulated by interferon-γ (IFN-γ) to mimic pSS-induced inflammation in SGs cells in vitro. Melatonin-treated mice exhibited a significant reduction in SG injury of NOD/Ltj mice, which was accompanied by an increase in salivary flow rate, a decrease in inflammatory infiltration within the gland, and a suppression of oxidative stress indicators as well as cell apoptosis. Notably, both melatonin membrane receptors and nuclear receptors played an important role in the anti-apoptotic effects of melatonin on the SGs of NOD/Ltj mice. Furthermore, melatonin blocked the IL-6/STAT3 pathway through receptor-dependent manners in IFN-γ-stimulated HSGE cells. However, it was evident that the anti-oxidative and anti-apoptotic properties of melatonin on IFN-γ-stimulated HSGE cells were diminished by IL-6 treatment. Melatonin had the potential to mitigate inflammation, oxidative stress, and apoptosis in SGs of pSS by inhibiting the IL-6/STAT3 pathway through receptor-dependent mechanisms. This intervention effectively prevented glandular damage and preserved functional integrity. [Display omitted] • Melatonin improved SG function and alleviated lymphocytic infiltration of SG in NOD mice. • Melatonin regulated expression and distribution of AQP5 in SGs of NOD mice, which might be the results of reduced cytokines. • Melatonin exerted protective effects on SGs of NOD mice by inhibiting IL-6/STAT3 pathway through receptor-dependent manner. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Implications of IFNγ SNP rs2069705 in primary Sjögren's syndrome: transcriptional activation and B cell infiltration.
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Chen, Xi, Li, Min, Li, Honglin, Liu, Miao, Su, Jianrong, and Ji, Yuzhu
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SJOGREN'S syndrome , *B cells , *IMMUNOPRECIPITATION , *SINGLE nucleotide polymorphisms , *GENE expression , *EXOCRINE glands , *PROTEIN-protein interactions - Abstract
Primary Sjögren's syndrome (pSS) is characterized by its autoimmune nature. This study investigates the role of the IFNγ SNP rs2069705 in modulating the susceptibility to pSS. Differential expression of IFNγ and BAFF was analyzed using the GEO database's mRNA microarray GSE84844. Genotyping of the IFNγ SNP rs2069705 was conducted via the dbSNP website. The JASPAR tool was used for predicting transcription factor bindings. Techniques such as dual-luciferase reporter assays, Chromatin immunoprecipitation, and analysis of a pSS mouse model were applied to study gene and protein interactions. A notable increase in the mutation frequency of IFNγ SNP rs2069705 was observed in MNCs from the exocrine glands of pSS mouse models. Bioinformatics analysis revealed elevated levels of IFNγ and BAFF in pSS samples. The model exhibited an increase in both CD20+ B cells and cells expressing IFNγ and BAFF. Knocking down IFNγ resulted in lowered BAFF expression and less lymphocyte infiltration, with BAFF overexpression reversing this suppression. Activation of the Janus kinase (JAK)/STAT1 pathway was found to enhance transcription in the BAFF promoter region, highlighting IFNγ's involvement in pSS. In addition, rs2069705 was shown to boost IFNγ transcription by promoting interaction between its promoter and STAT4. SNP rs2069705 in the IFNγ gene emerges as a pivotal element in pSS susceptibility, primarily by augmenting IFNγ transcription, activating the JAK/STAT1 pathway, and leading to B-lymphocyte infiltration in the exocrine glands. NEW & NOTEWORTHY: The research employed a combination of bioinformatics analysis, genotyping, and experimental models, providing a multifaceted approach to understanding the complex interactions in pSS. We have uncovered that the rs2069705 SNP significantly affects the transcription of IFNγ, leading to altered immune responses and B-lymphocyte activity in pSS. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Single-cell clonal tracing of glandular and circulating T cells identifies a population of CD9+ CD8+ T cells in primary Sjogren's syndrome.
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Chang, Ling, Zheng, Zihan, Xiao, Fan, Zhou, Yingbo, Zhong, Bing, Ni, Qingshan, Qian, Can, Chen, Chengshun, Che, Tiantian, Zhou, Yiwen, Zhao, Zihua, Zou, Qinghua, Li, Jingyi, Lu, Liwei, Zou, Liyun, and Wu, Yuzhang
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SJOGREN'S syndrome ,T cells ,CD8 antigen ,CELL populations ,EXOCRINE glands ,AUTOIMMUNE diseases - Abstract
Primary Sjogren's syndrome (pSS) is a complex chronic autoimmune disease in which local tissue damage in exocrine glands is combined with broader systemic involvement across the body in tissues including the skin. These combined manifestations negatively impact patient health and quality of life. While studies have previously reported differences in immune cell composition in the peripheral blood of pSS patients relative to healthy control subjects, a detailed immune cell landscape of the damaged exocrine glands of these patients remains lacking. Through single-cell transcriptomics and repertoire sequencing of immune cells in paired peripheral blood samples and salivary gland biopsies, we present here a preliminary picture of adaptive immune response in pSS. We characterize a number of points of divergence between circulating and glandular immune responses that have been hitherto underappreciated, and identify a novel population of CD8+ CD9+ cells with tissue-residential properties that are highly enriched in the salivary glands of pSS patients. Through comparative analyses with other sequencing data, we also observe a potential connection between these cells and the tissue-resident memory cells found in cutaneous vasculitis lesions. Together, these results indicate a potential role for CD8+ CD9+ cells in mediating glandular and systemic effects associated with pSS and other autoimmune disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Diagnostic and therapeutic potentials of extracellular vesicles for primary Sjögren's Syndrome: A review
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Arash Shahsavari and Fei Liu
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Primary Sjögren's syndrome ,Salivary diagnostics ,Extracellular vesicle ,MicroRNAs, Mesenchymal stem cells ,Immune modulation ,Dentistry ,RK1-715 - Abstract
Primary Sjögren syndrome (pSS) is a chronic autoimmune disease mainly affecting salivary and lacrimal glands. The current pSS biomarkers, serum autoantibodies, are negative in many pSS patients diagnosed with histopathology changes, indicating the need of novel biomarkers. The current therapies of pSS are merely short–term symptomatic relief and can't provide effective long–term remedy. Extracellular vehicles (EVs) are nano–sized lipid bilayer–delimited particles spontaneously released by almost all types of cells and carrying various bioactive molecules to mediate inter–cellular communications. Recent studies found that EVs from salivary gland epithelial cells and immune cells play essential roles in pSS pathogenesis. Correspondingly, EVs and their cargos in plasma and saliva are promising candidate biomarkers for pSS diagnosis. Moreover, EVs from mesenchymal stem cells have shown promises to improve pSS treatment by modulating immune responses. This review summarizes recent findings in roles of EVs in pSS pathogenesis, diagnosis, and treatment of pSS, as well as related challenges and future research directions.
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- 2024
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38. Serum biomarker-based risk model construction for primary Sjögren’s syndrome with interstitial lung disease
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Xiaoli Liu, Xia Zhang, Juan Shi, Shiqing Li, Xiuzhi Zhang, and Huiling Wang
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serum biomarkers ,cytokines ,primary Sjögren’s syndrome ,interstitial lung disease ,immune response ,Biology (General) ,QH301-705.5 - Abstract
BackgroundCytokine network disturbances in primary Sjögren’s syndrome (pSS) have been reported in many studies. However, their functions in patients with primary Sjögren’s syndrome and interstitial lung disease (pSS-ILD) is controversial. In this study, we aim to investigate the associations of immunological characteristics and cytokine profiles with pSS-ILD pathogenesis and explore their predictive values for pSS progression.MethodsA total of 256 patients initially diagnosed with pSS at Henan Provincial People’s Hospital were enrolled. After excluding the patients previously diagnosed with various serious acute and chronic respiratory system diseases and cases with other connective tissue diseases or congenital heart diseases, 94 pSS patients were included for further analysis, including 40 patients with ILD (pSS-ILD) and 54 patients without ILD (pSS-N-ILD). For comparison, 41 age- and sex-matched healthy individuals were included as normal controls. Their clinical symptoms and serological data including cyclic citrullinated peptide (CCP) antibody (anti-CCP), antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB, C-reactive protein, IgG, IgM, IgA, C3, C4, and 10 cytokines and chemokines were obtained. Wilcoxon test, chi-square test, Spearman correlation analysis, and logistics regression analysis were performed.ResultsHigher positive rates of anti-SSB and higher incidence of dry cough, dyspnea, and arthrosis symptoms were shown in pSS-ILD patients than in the pSS-N-ILD cases. Anti-CCP antibodies and cytokines (IL-1β, TNFα, IL-6, IL-5, IL-12p70, and IL-17) were higher, while C3 was lower in pSS-ILD patients than in pSS-N-ILD cases. Significant negative correlations of IgG with C3 and C4 and positive correlations of IL-12p70 and IL-17 with IL-6 were only shown in pSS-ILD patients. The anti-CCP antibody was positively correlated with IL-5 in pSS-ILD patients, but not in pSS-N-ILD cases. Multi-variable logistics regression analysis revealed the combination of anti-CCP, IL-17, IL-12p70, and IL-5 was effective in predicting the status of pSS-ILD in the pSS cases.ConclusionThere were significant differences in serum marker levels between pSS-ILD and pSS-N-ILD cases. The combination of anti-CCP, IL-17, IL-12p70, and IL-5 might be a potential risk predictor for pSS-ILD occurrence. The cytokines might be involved in the development and progression of pSS-ILD. These results would provide new therapeutic targets for pSS-ILD treatment.
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- 2024
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39. Corrigendum: Risk of primary Sjogren’s Syndrome following human papillomavirus infections: a nationwide population-based cohort study
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Huang-Hsi Chen, Kevin Sheng-Kai Ma, Chen Dong, Wen-Jung Chang, Kuan-Rong Gao, Wuu-Tsun Perng, Jing-Yang Huang, and James Cheng-Chung Wei
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Human papillomavirus ,infection ,autoimmunity ,primary Sjogren’s Syndrome ,cohort study ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2024
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40. BMS-986325 in Healthy Participants and Participants With Primary Sjögren's Syndrome
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- 2023
41. Seronegative primary Sjögren’s syndrome, a distinct subtype of primary Sjögren’s syndrome in Chinese patients
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Jingying Lan, Chaoqiong Deng, Heqing Huang, Peishi Rao, Yangchun Chen, Yingying Shi, Jie Chen, Guixiu Shi, Yuan Liu, and Shiju Chen
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Primary Sjogren’s syndrome ,Seronegative ,Heterogeneity ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background To investigate the clinical and immune characteristics of patients with primary Sjögren’s syndrome (pSS) who were negative for anti–Sjögren’s-syndrome-related antigen A antibodies (anti-SSA) and anti–Sjögren’s-syndrome-related antigen B antibodies (anti-SSB) in Chinese population. Methods A retrospective study were performed and 232 patients with pSS were analyzed. Patients positive for anti-SSA or/and anti-SSB were termed as seropositive pSS, and these negative for both anti-SSA and anti-SSB (non-antinuclear antibodies) as seronegative pSS. Clinical manifestations and laboratory findings were compared between the two groups. Results Among the 232 patients with pSS, 192 (82.8%) were seropositive pSS and 40 (17.2%) were seronegative pSS. Compared to seropositive pSS, seronegative pSS were older and with higher percentage of low disease activity (ESSDAI
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- 2024
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42. New‐onset primary Sjögren's syndrome following exposure to severe acute respiratory syndrome coronavirus 2: A retrospective cohort study
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Shu Liu, Jing Zhang, Mian Liu, Qun Chen, Shiying Wang, Dandan Wang, and Lingyun Sun
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ESSDAI ,primary Sjögren's syndrome ,SARS‐CoV‐2 ,vaccination ,Immunologic diseases. Allergy ,RC581-607 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Understanding the clinical implications of autoimmune manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is essential to reduce its consequences. This study was aimed at determining the activities of new‐onset primary Sjögren syndrome (pSS) since the emergence of SARS‐CoV‐2. Methods This retrospective cohort study included data from 471 participants with dry mouths and eyes who had been attending Nanjing Drum Tower Hospital since December 2019. By April 2023, patients diagnosed with pSS were sequentially assigned to vaccinated group (n = 24) or vaccinated and infected group based on exposure (n = 20). Patients diagnosed with pSS within 3 months of vaccination against SARS‐CoV‐2 were assigned to a vaccinated group, and those who had been vaccinated and then developed pSS within 3 months of follow up after direct exposure to SARS‐CoV‐2 were assigned to a vaccinated and infected group. The controls comprised age‐ and sex‐matched patients who had not been exposed to SARS‐CoV‐2 before December 2019 (n = 21). We then compared data among the three groups. Results The vaccinated and infected patients had more fever, malaise, splenomegaly, and weight loss before diagnosis and a higher European Alliance of Associations for Rheumatology Sjögren's syndrome disease activity index at the time of onset than the other two groups. Vaccinated patients had a higher frequency of anti‐nuclear antibody (ANA) titers > 1:320 (n = 12; 50%) and anti‐phospholipid antibodies (aPL) (n = 7; 29%) than the controls. The frequency of anti‐Ro/SSA antibodies (13, 65%), ANA titers > 1:320 (n = 16; 80%), and aPLs (n = 7; 29%) (n = 5; 25%) were all significantly higher in vaccinated patients with infection than those in the controls. Higher doses of glucocorticoids, cyclosporin A, and tacrolimus were administered to the vaccinated and infected than the vaccinated and control groups (p
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- 2024
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43. Hydroxychloroquine is associated with lower seroconversion upon 17DD-Yellow fever primovaccination in patients with primary Sjögren’s syndrome
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Ketty Lysie Libardi Lira Machado, Ismael Artur da Costa-Rocha, Laura Gonçalves Rodrigues Aguiar, Isac Ribeiro Moulaz, Samira Tatiyama Miyamoto, Priscila Costa Martins, Erica Vieira Serrano, Ana Paula Espíndula Gianordoli, Maria da Penha Gomes Gouvea, Maria de Fatima Bissoli, Sheila Maria Barbosa de Lima, Waleska Dias Schwarcz, Adriana de Souza Azevedo, Juliana Fernandes Amorim da Silva, Renata Tourinho Santos, Joaquim Pedro Brito-de-Sousa, Jordana Grazziela Coelho-dos-Reis, Ana Carolina Campi-Azevedo, Andréa Teixeira-Carvalho, Vanessa Peruhype-Magalhães, Francieli Fontana Sutile Tardetti Fantinato, Licia Maria Henrique da Mota, Olindo Assis Martins-Filho, and Valéria Valim
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Primary Sjögren’s syndrome ,hydroxychloroquine ,17DD-YF vaccine ,humoral immunity ,serum biomarkers ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren’s syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3–4/Day5–6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14–28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.
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- 2024
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44. Development of a nomogram for membranous nephropathy prediction in patients with primary Sjögren's syndrome: a 6-year retrospective study.
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Lihui Guo, Shan Zhao, and Xudong Liu
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SJOGREN'S syndrome ,NOMOGRAPHY (Mathematics) ,RHEUMATOID factor ,LEUCOCYTES ,ANTINUCLEAR factors - Abstract
Objectives: Nephritis is a life-threatening complication of primary Sjögren's syndrome (pSS), with membranous nephropathy (MN) being prevalent. Renal biopsy is the gold standard for MN diagnosis, but it is invasive and cannot be repeatedly performed. This study aimed to develop a nomogram for the prediction of MN in patients with pSS. Methods: This retrospective study included patients with pSS admitted to the Rheumatology and Immunology Department of the First Affiliated Hospital of China Medical University between January 2015 and January 2021. A nomogram was developed using multivariable logistic regression analysis and evaluated using receiver operating characteristic (ROC) curve analysis. Bootstrap resampling analysis (1,000 times) was performed to evaluate the nomogram for discrimination and the calibration curve for consistency. Results: A total of 237 patients with pSS [aged 53.00 (44.00, 61.00) years] were included, with 35 pSS-MN patients. Based on clinical practice and multivariable logistic regression analysis, seven variables associated with pSS-MN were selected, including white blood cells, creatine, complement 3, rheumatoid factor, antinuclear antibodies, anti-SSA antibody, and interstitial lung disease. The area under the ROC curve was 0.860 (95% confidence interval: 0.796-0.919), indicating good predictive power. In addition, the nomogram exhibited excellent performance, as demonstrated by the calibration curve and decision curve analysis. Conclusion: This study developed a risk prediction nomogram for MN in patients with pSS, with high predictive power. It may be used to improve the management of patients with pSS. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Data-lndependent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sjogren's Syndrome.
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Tian, Yi-Chao, Guo, Chun-Lan, Li, Zhen, You, Xin, Liu, Xiao-Yan, Su, Jin-Mei, Zhao, Si-Jia, Mu, Yue, Sun, Wei, and Li, Qian
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SJOGREN'S syndrome , *BIOMARKERS , *SALIVARY glands , *RANDOM forest algorithms , *QUANTITATIVE research - Abstract
As primary Sjogren's syndrome (pSS) primarily affects the salivary glands, saliva can serve as an indicator of the glands' pathophysiology and the disease's status. This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. The discovery set contained 49 samples (24 from pSS and 25 from age- and gender-matched healthy controls [HCs]) and the validation set included 25 samples (12 from pSS and 13 from HCs). Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio. Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition (DIA) strategy on a 2D LC–HRMS/MS platform to reveal differential proteins. The crucial proteins were verified using DIA analysis and annotated using gene ontology (GO) and International Pharmaceutical Abstracts (IPA) analysis. A prediction model for SS was established using random forests. A total of 1,963 proteins were discovered, and 136 proteins exhibited differential representation in pSS patients. The bioinformatic research indicated that these proteins were primarily linked to immunological functions, metabolism, and inflammation. A panel of 19 protein biomarkers was identified by ranking order based on P -value and random forest algorichm, and was validated as the predictive biomarkers exhibiting good performance with area under the curve (AUC) of 0.817 for discovery set and 0.882 for validation set. The candidate protein panel discovered may aid in pSS diagnosis. Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients. DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome. [ABSTRACT FROM AUTHOR]
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- 2024
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46. Identification and verification of inflammatory biomarkers for primary Sjögren's syndrome.
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Liu, Xiaodan, Wang, Haojie, Wang, Xiao, Jiang, Xiaodan, Jin, Yinji, Han, Ying, and Zhang, Zhihui
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SJOGREN'S syndrome , *T helper cells , *REGULATORY T cells , *IMMUNOLOGIC memory , *BIOMARKERS - Abstract
Introduction: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by inflammatory infiltration, and dysfunction of the salivary and lacrimal glands. This research aimed to explore the disease pathogenesis and improve the diagnosis and treatment of pSS by mining inflammation-associated biomarkers. Methods: Five pSS-related datasets were retrieved from the Gene Expression Omnibus (GEO) database. Inflammation-associated biomarkers were determined by the least absolute shrinkage and selection operator (LASSO) and support vector machines recursive feature elimination (SVM-RFE). Single sample gene set enrichment analysis (ssGSEA) was implemented to profile the infiltration levels of immune cells. Real-time quantitative PCR (RT-qPCR) verified the expression of biomarkers in clinical samples. Results: Four genes (LY6E, EIF2AK2, IL15, and CXCL10) were screened as inflammation-associated biomarkers in pSS, the predictive performance of which were determined among three pSS-related datasets (AUC > 0.7). Functional enrichment results suggested that the biomarkers were involved in immune and inflammation-related pathways. Immune infiltration analysis revealed that biomarkers were notably connected with type 2 T helper cells, regulatory T cells which were significantly expressed between pSS and control. TESTOSTERONE and CYCLOSPORINE were predicted to take effect by targeting CXCL10 and IL15 in pSS, respectively. Conclusion: Four inflammation-associated biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were explored, and the underlying regulatory mechanisms and targeted drugs associated with these biomarkers were preliminarily investigated according to a series of bioinformatics methods based on the online datasets of pSS, which provided a reference for understanding the pathogenesis of pSS. Key Points • Inflammation-associated biomarkers (LY6E, EIF2AK2, IL15, and CXCL10) were firstly identified in Sjögren's syndrome based on LASSO and SVM-RFE analyses. • CXCL10, EIF2AK2 and LY6E were prominently positively correlated with immature B cells, while IL15 were significantly negatively correlated with memory B cells in Sjögren's syndrome. • LY6E, EIF2AK2, IL15, and CXCL10 were significantly more highly expressed in clinical Sjögren's syndrome samples compared to healthy control samples, which was consistent with the analysis results of the GEO database. •LY6E, EIF2AK2, IL15, and CXCL10 might be used as the biomarkers for the treatment and diagnosis of Sjögren's syndrome. [ABSTRACT FROM AUTHOR]
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- 2024
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47. Predicting the risk of interstitial lung disease in patients with primary Sjögren's syndrome: Novel nomogram and elevated Th2 cells.
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Wang, Yanlin, Jia, Yuhan, Qin, Yan, Feng, Min, Liang, Zhaojun, Zhao, Xiangcong, Gao, Chong, Guo, Hui, and Luo, Jing
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SJOGREN'S syndrome , *TH2 cells , *INTERSTITIAL lung diseases , *LEUCOCYTES , *NOMOGRAPHY (Mathematics) - Abstract
Interstitial lung disease (ILD) is one of the most common pulmonary complications in patients with primary Sjögren's syndrome (pSS). This study was performed to identify immunological risk factors of pSS-associated ILD (pSS-ILD) and to further establish and evaluate of nomograms predicting the risk of ILD in patients with pSS. A total of 622 patients with pSS (117 with ILD and 505 without lung involvement) and 166 healthy control subjects (HCs) were ultimately recruited to this retrospective study. Routine examination indicators, tumour markers and lymphocyte (LYMP) subpopulations were extracted. Simple and multiple logistic regressions analyses were performed to screen for independent predictors. Restricted cubic splines were used to examine associations of independent predictors with ILD, and a risk assessment model was constructed. A nomogram prediction model was developed, and receiver operating characteristic (ROC) curve analysis was performed to assess its performance. Univariate and multivariate logistic regression analyses showed that the older age, white blood cell (WBC) count, haemoglobin (HB) level, albumin (ALB) level, CA242 level, and the C-reactive protein (CRP)/LYMP ratio (CLR) were independent predictors of pSS-ILD in a linear manner, these factors were integrated and used to construct a nomogram prediction model. The model had clinical predictive value. In addition, the elevated Th2 cells proportion in pSS patients was significantly positively correlated with lung involvement, while it was negatively correlated with HB and ALB levels. Remarkably, the numbers of Th2 cells were correlated with the CLR in both pSS patients and those with pSS-ILD. Our novel ILD nomogram could be used to assess the risk of ILD in pSS patients with good discrimination ability. As well as, elevated peripheral blood Th2 cell levels may be related to ILD in patients with pSS. • Inflammatory indexes and tumor markers were elevated in pSS-ILD patients. • Development and validation of nomogram for prediction of ILD in pSS. • Elevated Th2 cell proportion was associated with lung involvement in pSS patients. [ABSTRACT FROM AUTHOR]
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- 2024
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48. The proportion of CD161 on CD56+ NK cells in peripheral circulation associates with clinical features and disease activity of primary Sjögren's syndrome.
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Zhao, Ping, Yang, Yanhong, Song, Saizhe, Cheng, Wei, Peng, Cheng, Chang, Xin, Wu, Jian, and Liu, Cuiping
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KILLER cells , *SJOGREN'S syndrome , *PERIPHERAL circulation , *BILIARY liver cirrhosis , *LEUCOCYTES , *JOINT pain , *RECEIVER operating characteristic curves - Abstract
Objectives: The purpose of this study was to examine the proportion of CD161 on CD56+ natural killer (NK) cells in peripheral blood of primary Sjögren's syndrome (pSS) and investigate its clinical relevance of pSS. Methods: The proportion of CD56+ NK cells and CD161 on CD56+ NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between the proportion of CD161+CD56+ NK cells and clinical features and disease activity of pSS were further analyzed. Meanwhile, we drew the receiver operating characteristic curve to evaluate the diagnostic value of CD161+CD56+ NK cells in pSS. In addition, we evaluated the differences in the effects of CD161+ cells and CD161− cells in peripheral blood on the function of CD56+ NK cells in 5 pSS patients. Results: The proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased markedly in pSS patients compared to HCs. The correlation analysis showed that the proportion of CD161+CD56+ NK cells negatively correlated with white blood cells, Immunoglobulin A (IgA), IgM, IgG, European League Against Rheumatism Sjogren's Syndrome Patient Reported Index and European League Against Rheumatism Sjogren's Syndrome Disease Activity Index, and positively correlated with complement C4. The proportion of CD161+CD56+ NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis, interstitial lung disease, anti‐SSA/Ro60 positive, anti‐SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with inactive patients, the proportion of CD161+CD56+ NK cells decreased obviously in active patients. The area under the curve was 0.7375 (p =.0016), the results indicated that CD161+CD56+ NK cells had certain diagnostic values for pSS. In addition, the proportion of CD86, HLA‐DR, Ki67, FasL, TNF‐α, and IFN‐γ on CD161+CD56+ NK cells was lower than that on CD161−CD56+ NK cells in the peripheral blood of pSS patients. Conclusion: This study suggested that the proportion of CD56+ NK cells and CD161+CD56+ NK cells decreased significantly in pSS patients, and the proportion of CD161+CD56+ NK cells negatively associated with the clinical features and disease activity of pSS patients. CD161 expression inhibited the function of CD56+ NK cells in peripheral blood of pSS patients. The CD161+CD56+ NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS. [ABSTRACT FROM AUTHOR]
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- 2024
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49. The Physical and Psychosocial Impact of Fatigue among Patients with Sjogren's Syndrome: A Systematic Review.
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Mardale, Denise-Ani, Opriș-Belinski, Daniela, Bojincă, Violeta, Bojincă, Mihai, Mazilu, Diana, Păsăran, Emilia, Nițăa, Cristina, Groșeanu, Laura, Berghea, Florian, and Bălănescu, Andra-Rodica
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SJOGREN'S syndrome , *FATIGUE (Physiology) , *CANCER fatigue , *SLEEP interruptions , *EXECUTIVE function , *LACRIMAL apparatus - Abstract
Background: Primary Sjögren's syndrome (pSS) is a complex autoimmune disorder characterized by organ-specific symptoms in the salivary and lacrimal glands, as well as systemic manifestations. Fatigue, a prominent aspect, significantly influences the overall quality of life for individuals with pSS. Methods: This review seeks to evaluate the impact of fatigue by exploring its consequences, potential causes, and effects on physical and psychological well-being, while also investigating its management strategies. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review involved a five-step algorithm. Initially identifying 78 articles in reputable international medical databases, we applied eligibility criteria and removed duplicates, resulting in 19 articles for qualitative synthesis. Results: This review delves into the predictive factors for heightened fatigue in pSS, encompassing rheumatoid factor levels, erythrocyte sedimentation rate, and immunoglobulin G levels. Sleep disturbances, specifically nighttime pain and nocturia, emerged as determinants of persistent daytime fatigue. Cognitive impairment in pSS involves deteriorations in global memory, executive functioning, and attentional resources. Furthermore, functional limitations in pSS impact patients' quality of life. Conclusions: The significance of fatigue in pSS, its consequences, and profound influence on the quality of life necessitate further research for a more comprehensive understanding of this complex issue. [ABSTRACT FROM AUTHOR]
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- 2024
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50. Nephrolithiasis and/or nephrocalcinosis is significantly related to renal dysfunction in patients with primary Sjögren's syndrome.
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Yuhei Fujisawa, Ichiro Mizushima, Yasunori Suzuki, and Mitsuhiro Kawano
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SJOGREN'S syndrome , *KIDNEY diseases , *KIDNEY stones , *KIDNEY calcification , *HEART block , *GLOMERULAR filtration rate , *ACID-base imbalances - Abstract
Objective: The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. Methods: The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody–positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. Results: Of the 68 patients with anti-SSA-antibody–positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary β2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. Conclusion: Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS. [ABSTRACT FROM AUTHOR]
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- 2024
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