Search

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.

Objective: This study aims to establish and evaluate a risk prediction model for coronary heart disease (CHD) in patients with primary Sjögren's syndrome (pSS) based on peripheral blood levels of interleukin-6 (IL-6) and the percentage of regulatory T cells (Treg%). This model is intended to facilitate the timely identification of high-risk patients and the implementation of preventive measures. Methods: Clinical data were collected from 120 pSS patients who visited the Second Hospital of Shanxi Medical University between November 2021 and September 2023. Patients were classified into pSS and pSS-CHD groups according to CHD diagnostic criteria. Peripheral blood lymphocyte subsets and cytokine levels were assessed using flow cytometry. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, and a nomogram was constructed based on these factors. The model's discriminatory ability, calibration, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. Results: The univariate and multivariate logistic regression analyses identified several independent risk factors for CHD in pSS patients: erythrocyte sedimentation rate (ESR) (OR=1.10, P=0.019), triglycerides (TG) (OR=3.67, P=0.041), IL-6 (OR=1.29, P=0.048), and Treg% (OR=0.25, P=0.004). A nomogram incorporating these factors demonstrated an area under the curve (AUC) of 0.96, indicating excellent predictive performance, and showed good calibration (P=0.599), suggesting significant clinical applicability. Furthermore, Treg% exhibited a negative correlation with cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C) levels, while IL-6 showed a positive correlation with CHOL and LDL-C levels. TG was positively correlated with C-reactive protein (CRP). Conclusion: This study successfully developed a risk prediction model based on peripheral blood IL-6 and Treg% levels, providing critical evidence for the early identification and personalized prevention of CHD in pSS patients, with potential clinical implications. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) involvement can occur in primary Sjögren's syndrome (pSS) due to co-existing neuromyelitis optica spectrum disorder (NMOSD) which has a highly relapsing course requiring indefinite immunosuppression, and if not diagnosed early, damage accrual occurs over time leading to permanent disability and morbidity. In this review, we describe and outline the clinical course and outcomes of anti-aquaporin 4 (AQP4) antibody seropositive NMOSD with pSS overlap cases. To investigate the co-existence of AQP4 + NMOSD with pSS, we conducted a review of individual patient data from case reports and case series found in major databases. The study extracted clinico-demographic features, imaging and laboratory profiles, treatment approaches, and outcomes of these patients. Inclusion criteria for the review required patients to have positivity for anti-AQP4 or NMO-IgG autoantibodies in the blood and/or cerebrospinal fluid (CSF) and exhibit at least one manifestation of both pSS and NMOSD. In this overlap between AQP4 + NMOSD and pSS, 44 patients were included of whom 41 (93.2%) were females. The mean age of pSS onset was 44.8 ± 18.4 years and NMOSD onset was 43.2 ± 19.8 years. In 20 (45.5%) patients, NMOSD preceded pSS onset, 13 (29.5%) NMOSD occurred after pSS onset, and 11 (25%) patients had a simultaneous presentation. 31 (70.5%) patients experienced acute transverse myelitis, 21 (47.7%) optic neuritis, 14 (31.8%) cerebral syndrome, 10 (22.7%) acute brainstem syndrome, 5 (11.4%) area postrema syndrome, and 2 (4.5%) diencephalic clinical syndromes. For the treatment of acute phase, 40 (90.9%) patients received intravenous methylprednisolone, 15 (34.1%) received plasma exchange, and 10 (22.7%) received intravenous immunoglobulin; and for the induction/maintenance therapy, 16 (36.4%) patients received cyclophosphamide, 6 (13.6%) received rituximab, 16 (36.4%) received azathioprine, and 10 (22.7%) received mycophenolate mofetil. Disease course was monophasic in 2 (4.5%) and relapsing in 27 (61.4%) patients. At median (IQR) follow-up duration of 2.4 (6) years, 39 (88.6%) patients showed improvement, 3 (6.8%) showed stabilization and 2 (4.5%) showed worsening of their NMOSD manifestations. In this overlap syndrome of AQP4 + NMOSD and pSS, patients have a neurologically disabling disorder that can mimic neurological manifestations of pSS, frequently occurs prior to the onset of pSS, has a relapsing course, responds well to immunosuppressants, and necessitates indefinite treatment. Collaborative multicentre studies are needed to clarify the natural history and outcomes of this rare overlap syndrome. [ABSTRACT FROM AUTHOR]

The study aims to assess the diagnostic and clinical significance of autoantibodies against aquaporin-1 (anti-AQP1) and aquaporin-5 (anti-AQP5) in primary Sjögren's syndrome (pSS). A total of 163 participants were categorized into three groups: pSS group, other connective tissue diseases (CTD) group, and healthy control (HC) group. The levels of anti-AQP1 and anti-AQP5 autoantibodies in serum were determined using enzyme-linked immunosorbent assay (ELISA), and clinical data from patients were collected for statistical analysis. Our results showed that the level of anti-AQP1 in the pSS group was higher than in the HC group (P < 0.05), and no significant difference was observed between the pSS group and the CTD group (P > 0.05). ROC showed that the anti-AQP1 had no diagnostic value for pSS (P > 0.05). The anti-AQP5 level of 39 healthy adults was all below the cut-off value (14.10 ng/ml) (P < 0.05). The level of anti-AQP5 in the pSS group was higher than the CTD group (P < 0.05), the AUC was 0.86 (95% CI 0.80–0.93), with a sensitivity of 0.95 (95% CI 0.87–0.99) and a specificity of 0.70 (95% CI 0.58–0.84). No correlation was found between anti-AQP5 levels and the EULAR primary Sjögren's syndrome disease activity index score, anti-SSA, anti-SSB, antinuclear antibodies, rheumatoid factor, anti-ds-DNA, salivary gland flow rate, complement 3, and lymphocyte count in pSS samples (P > 0.05), respectively. Therefore, the elevated anti-AQP5 may emerge as a novel diagnostic biomarker for pSS patients due to high sensitivity and specificity. Key Points • The elevated anti-AQP5 may emerge as a novel diagnostic biomarker for pSS patients due to high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Objectives: Low-dose interleukin 2 (Ld-IL2) is increasingly being explored as an immune-modulating treatment for autoimmune diseases which mainly affect T cell subsets. This study investigates the metabolic effects of Ld-IL2 therapy in patients with primary Sjögren's syndrome (pSS). Method: A total of 60 patients were recruited to conduct a double-blind, randomized clinical trial. Of these patients, 50% (30/60) received Ld-IL2 therapy along with standard treatment for 12 weeks, followed by 12 weeks of follow-up. The effectiveness was evaluated by Sjögren's Tool for Assessing Response (STAR). An untargeted analysis was performed to profile hydrophilic metabolites. Results: Metabolic profiling revealed significant alterations post-treatment, notably in metabolites like acetyl-CoA, ascorbic acid, and glutathione, which are beneficial in managing autoimmune diseases. In addition, the levels of metabolite accumulation were correlated with variations in immune cell subsets (p < 0.05), particularly Tregs. Moreover, patients exhibiting a specific metabolic profile, including lower serum levels of isoleucine, ADP, Thymidine 5'-triphosphate, and other metabolites, had a high response rate (91.7%-98.6%), as indicated by the receiver operating characteristic (ROC) curve. Conclusions: These findings suggest that Ld-IL2 therapy influences metabolic pathways in pSS, offering insights into the systemic effects of Ld-IL2 therapy beyond immune modulation. Trial registration number: ClinicalTrials.gov number, NCT02464319. Key Points • Metabolic alteration in pSS is significantly associated with Ld-IL2 therapy. • Metabolic changes correlate with variations in immune cell subsets, particularly Tregs. • Metabolic profiling could be a valuable tool in guiding Ld-IL2 therapy choices for pSS patients. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to evaluate the factors influencing the referral delay in patients with primary Sjogren's syndrome (Sjogren's) and systemic sclerosis (SSc). Materials and Methods: The independent, multicentre, cross-sectional study collected data from seven centres across India through the Indian Rheumatology Association (IRA) database. The patient-related factors and referral factors were determined based on the patient narrations. Based on the patient's income, a modified version of the Prasad scale was employed to classify them according to socioeconomic status. Results: The study included 118 patients with Sjogren's and 166 patients with SSc. Approximately 60% of patients with SSc and Sjogren's received rheumatology specialty care more than 6 months after symptom onset. The primary reasons for this delay were identified as a lack of awareness of rheumatology specialty care among patients (Sjogren's: 61%; SSc: 74%) and disease management by other specialists (Sjogren's: 75%; SSc: 62%) rather than rheumatologists. Additionally, over 25% of primary care practitioners were unaware of rheumatology specialty services, and a similar percentage of patients were not diagnosed with rheumatic diseases by their primary care physicians. Patients with delayed referrals for Sjogren's exhibited higher rates of haematologic, oral, and non-articular pain. Similarly, in SSc patients, delayed referral was associated with a significantly higher prevalence of skin involvement (P <.01). Conclusion: Patient referrals to other specialties and a lack of knowledge about rheumatology were the primary causes of referral delays. Educating primary care physicians and facilitating direct referrals to rheumatology specialists could help reduce these delays. The study findings may help in stratifying interventions to improve early referral and access to rheumatology specialty care for patients with Sjogren's and SSc. [ABSTRACT FROM AUTHOR]

To investigate if salivary O-linked glycans are altered in primary Sjögren’s syndrome (pSS), and thus contributing to explain symptoms of oral dryness, and an impaired oral mucosal barrier function leading to changes in microbial metabolism and colonization by both pathogenic and commensal microorganisms and increased prevalence of oral diseases. O-linked oligosaccharides from stimulated whole saliva (SWS) samples from 24 patients with pSS, 38 patients with non-pSS sicca, and 23 healthy controls were analyzed using liquid chromatography mass spectrometer (LC-MS). Non-fractionated reduced and alkylated saliva was dot-blotted to PVDF-membrane and O-linked oligosaccharides were released using reductive beta-elimination. The 50 most abundant glycans were identified and their intensity compared for each sample, reflecting the relative abundance of individual monosaccharide residues. Comparison of the compositions of O-glycans in SWS samples revealed higher relative levels of sialic acid (NeuAc) and lower levels of neutral amino-monosaccharides (HexNAc) in pSS and non-pSS sicca patients than in the healthy controls. MS2 fragmentation analysis of salivary O-glycans suggests that altered sulfation, fucosylation, sialylation and distribution of core types may all contribute to the observed alteration, directly or indirectly. Additionally, the short disaccharide sialyl-Tn was most abundant in the saliva samples from patients with pSS. Our findings indicate that the salivary mucin-type O-glycan profile is altered in pSS, reflecting a dysfunction of the post-translational modification of salivary mucins leading to rheological changes of saliva, oral dryness symptoms, and impaired oral mucosal barrier function. The pathophysiological significance of the aberrant O-glycosylation needs further elucidation. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Primary Sjögren's syndrome (pSS) are at a higher risk of thyroid disorders than the general population. This retrospective analysis of 202 patients with pSS was conducted to uncover risk factors associated with thyroid involvement and to create a predictive model for this condition. Methods: We analyzed 202 patients with pSS from Guang'anmen Hospital, China Academy of Chinese Medical Sciences, with 105 cases of thyroid involvement and 97 without. The Least Absolute Shrinkage and Selection Operator method was used to identify key variables for our risk model. These variables were then subjected to multivariate logistic regression to develop the model. The accuracy of the model was assessed through the C-index, receiver operating characteristic curves, calibration plots, and decision curve analysis, with internal validation via bootstrapping. Results: High-sensitivity C-reactive protein (HCRP), pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and aspartate aminotransferase (AST) were incorporated into the nomogram. The model showed robust discrimination and calibration abilities. Decision curve analysis indicated the clinical utility of our nomogram in intervening on the probability thresholds of thyroid disease. Conclusion: By integrating HCRP, pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and AST, our thyroid risk nomogram can predict the risk of thyroid involvement in patients with pSS, aiding in more informed treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by the destruction of exocrine glands primarily via T‐cell‐mediated B‐cell over‐activation and cytokine production. This leads to pronounced dryness of the mouth and eyes and can result in multi‐systemic involvement affecting the kidneys, lungs, and blood. In recent years, there has been increasing attention on the role of immune cells in pSS. However, studies investigating the causal role of immune cells in pSS have been relatively limited. Methods: In this study, we employed a two‐way two‐sample Mendelian randomization approach to assess the causal relationship between immune cells and pSS. Utilizing publicly available genome‐wide association study (GWAS) data, we explored the causal links between 731 immunophenotypically labeled immune cells and the risk of pSS. Results: Through the use of instrumental variables derived from GWAS data and corrected for false discovery rate (FDR), we identified three immune cells with increased levels that were causally associated with pSS risk (FDR < 0.05). These included IgD+ CD38br AC B cells, CD27 on IgD+ CD38− unswitched memory B cells, and Granulocyte % leukocyte. Additionally, three immune cells with reduced levels were found to be causally associated with pSS risk, namely CD4+ CD8dim %lymphocyte, CD4+ CD8dim %leukocyte, and CD28 on activated and secreting regulatory T cells (Tregs). Furthermore, the development of pSS was associated with elevated levels of CD33br HLA DR+ CD14− % CD33br HLA DR+ in myeloid cells. Conclusion: This study demonstrates that immune responses influence the progression of pSS in a complex pattern. Our findings may provide new insights into the immunology of pSS pathogenesis and more experimental studies should be conducted to further explore the potential mechanisms between identified immune features and pSS risk, which may provide a basis for exploring early intervention methods for pSS and developing targeted therapeutic strategies or even reshaping immune homeostasis. [ABSTRACT FROM AUTHOR]

Background: This study investigates the clinical characteristics and differences between primary Sjögren's Syndrome (pSS) and secondary Sjögren's Syndrome (sSS) in a cohort of 50 patients. Methods: Conducted across two academic facilities in North-East Romania, the study emphasizes the importance of glandular and extraglandular manifestations, focusing on salivary flow rates, pH levels, and buffer capacity. Patients were diagnosed using the 2016 ACR-EULAR classification criteria, with a detailed examination including salivary tests, biopsies, and antibody presence. Results: The findings highlight significant differences between pSS and sSS, particularly in salivary function, with pSS patients exhibiting more severe glandular dysfunction. The study also notes a higher prevalence of inflammatory joint involvement in sSS patients, often associated with rheumatoid arthritis. Statistical analysis revealed correlations between salivary parameters and disease progression, underscoring the necessity of tailored treatment strategies. The research suggests that lower salivary flow rates and altered pH levels in pSS patients contribute to compromised oral health, including increased dental cavities and periodontal disease. Conclusions: The study's results contribute to a deeper understanding of Sjögren's Syndrome and reinforce the need for multidisciplinary management to address both systemic and oral health complications in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate dry eye severity and ocular surface inflammation in autoimmune rheumatic diseases (ARDs). Methods: Seventy-nine patients with ARDs were enrolled, including 26 patients with rheumatoid arthritis (RA), 33 patients with systemic lupus erythematosus (SLE), and 20 patients with primary Sjögren's syndrome (pSS). All patients underwent ocular surface evaluations, including ocular surface symptoms, signs, conjunctival impression cytology, and tear multicytokine detection. Systemic conditions, including disease duration, disease activity, and serological parameters, were also noted. Results: SLE patients had the shortest disease duration, and nearly half of them had low disease activity, while RA patients and pSS patients had a relatively long disease duration, and approximately 90% of them had moderate or high disease activity. The incidence of dry eye and the levels of the proinflammatory tear cytokines in SLE were significantly lower than those in RA and pSS. However, ocular surface squamous metaplasia was more severe in SLE and pSS than in RA. Dry eye severity in all ARD patients was shown to be independent of disease activity, while Nelson's grades were positively correlated with disease duration in RA patients. Disease-related serological parameters were associated with tear proinflammatory cytokines in all ARD patients. Conclusions: Variable degrees of dry eye and immune-mediated ocular surface inflammation persist in different ARD patients. In addition to a well-known association between dry eye and pSS, dry eye is also commonly observed in SLE and RA patients. Therefore, there is a definite need for regular ophthalmologic evaluations and topical medications in all patients with ARDs. [ABSTRACT FROM AUTHOR]

To assess the efficacy of methotrexate (MTX) and hydroxychloroquine (HCQ) in improving fatigue symptoms in patients with primary Sjögren's syndrome (pSS). Methods: A single-center retrospective study was conducted on pSS patients experiencing fatigue symptoms. All patients received either MTX, HCQ, or a combination of MTX + HCQ for a period of six months. Clinical efficacy was measured using the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), fatigue severity scale (FSS), and visual analog scale (VAS) score. These measures were assessed at baseline and at 1, 2, 3, and 6 months. Results: A total of 86 pSS patients with fatigue symptoms were enrolled (27 received MTX, 29 received HCQ, and 30 received MTX + HCQ). Patients receiving MTX and MTX + HCQ showed significant improvements at 6th month in ESSDAI, ESSPRI, FSS, FACIT-F, and VAS scores (all P < 0.01) compared with baseline. Repeated-measures analysis of variance revealed that patients treated with MTX and MTX + HCQ experienced significant improvements in ESSDAI, FSS, FACIT-F, and VAS scores (all P < 0.01) from baseline to the 6th month. The HCQ group did not show significant improvement in FSS, FACIT-F, and VAS scores (all P > 0.05), although their ESSDAI and ESSPRI scores did improve significantly (all P < 0.01). Patients in the MTX group showed the most improvement in mean changes of ESSDAI score, FSS score, FACIT-F score, and VAS score from baseline to the 6th month. And patients received MTX treatment significantly had more fatigue remission numbers (all P < 0.05). Conclusion: In clinical practice, methotrexate is more effective than hydroxychloroquine in improving fatigue symptoms, as measured by patient-reported fatigue scales (FSS, FACIT-F, and VAS scores) in patients with pSS. [ABSTRACT FROM AUTHOR]

Abstract To investigate if salivary O-linked glycans are altered in primary Sjögren’s syndrome (pSS), and thus contributing to explain symptoms of oral dryness, and an impaired oral mucosal barrier function leading to changes in microbial metabolism and colonization by both pathogenic and commensal microorganisms and increased prevalence of oral diseases. O-linked oligosaccharides from stimulated whole saliva (SWS) samples from 24 patients with pSS, 38 patients with non-pSS sicca, and 23 healthy controls were analyzed using liquid chromatography mass spectrometer (LC-MS). Non-fractionated reduced and alkylated saliva was dot-blotted to PVDF-membrane and O-linked oligosaccharides were released using reductive beta-elimination. The 50 most abundant glycans were identified and their intensity compared for each sample, reflecting the relative abundance of individual monosaccharide residues. Comparison of the compositions of O-glycans in SWS samples revealed higher relative levels of sialic acid (NeuAc) and lower levels of neutral amino-monosaccharides (HexNAc) in pSS and non-pSS sicca patients than in the healthy controls. MS2 fragmentation analysis of salivary O-glycans suggests that altered sulfation, fucosylation, sialylation and distribution of core types may all contribute to the observed alteration, directly or indirectly. Additionally, the short disaccharide sialyl-Tn was most abundant in the saliva samples from patients with pSS. Our findings indicate that the salivary mucin-type O-glycan profile is altered in pSS, reflecting a dysfunction of the post-translational modification of salivary mucins leading to rheological changes of saliva, oral dryness symptoms, and impaired oral mucosal barrier function. The pathophysiological significance of the aberrant O-glycosylation needs further elucidation.

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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

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.

Bowen Wei,1,2,&ast; Qingyun Yue,1,2,&ast; Yuxiu Ka,1,2,&ast; 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&ast;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

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.

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

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]

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]

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]

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]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

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]

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]

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]

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]

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]

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.

ObjectiveThis study aims to establish and evaluate a risk prediction model for coronary heart disease (CHD) in patients with primary Sjögren’s syndrome (pSS) based on peripheral blood levels of interleukin-6 (IL-6) and the percentage of regulatory T cells (Treg%). This model is intended to facilitate the timely identification of high-risk patients and the implementation of preventive measures.MethodsClinical data were collected from 120 pSS patients who visited the Second Hospital of Shanxi Medical University between November 2021 and September 2023. Patients were classified into pSS and pSS-CHD groups according to CHD diagnostic criteria. Peripheral blood lymphocyte subsets and cytokine levels were assessed using flow cytometry. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, and a nomogram was constructed based on these factors. The model’s discriminatory ability, calibration, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis.ResultsThe univariate and multivariate logistic regression analyses identified several independent risk factors for CHD in pSS patients: erythrocyte sedimentation rate (ESR) (OR=1.10, P=0.019), triglycerides (TG) (OR=3.67, P=0.041), IL-6 (OR=1.29, P=0.048), and Treg% (OR=0.25, P=0.004). A nomogram incorporating these factors demonstrated an area under the curve (AUC) of 0.96, indicating excellent predictive performance, and showed good calibration (P=0.599), suggesting significant clinical applicability. Furthermore, Treg% exhibited a negative correlation with cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C) levels, while IL-6 showed a positive correlation with CHOL and LDL-C levels. TG was positively correlated with C-reactive protein (CRP).ConclusionThis study successfully developed a risk prediction model based on peripheral blood IL-6 and Treg% levels, providing critical evidence for the early identification and personalized prevention of CHD in pSS patients, with potential clinical implications.

Background: Primary Sjogren's syndrome (pSS) is a common chronic autoimmune disease that presents limited treatment options and poses significant challenges for patients. Maidong Dishao Decoction (MDDST), a traditional Chinese medicine compound, has demonstrated potential in alleviating dryness symptoms associated with pSS. Therefore, it is important to study the specific mechanism of its therapeutic effect. Objective: This study aims to investigate the effects of MDDST on gut microbiota, short-chain fatty acids (SCFAs), and the Th17/Treg immune balance in non-obese diabetes (NOD) mice. Methods: The study employed ultrahigh-performance liquid chromatography coupled with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) to identify the primary components of MDDST. Subsequently, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assays (ELISA), and flow cytometry analyses were conducted to evaluate the therapeutic effects of MDDST in NOD mice. Additionally, 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS) were utilized to assess the influence of MDDST on gut microbiota and SCFAs. Finally, fecal microbiota transplantation (FMT) and SCFA-based interventions were performed to elucidate the mechanisms through which MDDST exerts its effects. Results: The research findings demonstrate that MDDST exerts therapeutic effects on NOD mice, primarily manifested as reduced inflammation, decreased water intake, ameliorated pathological changes and lowered levels of Sjogren's syndrome antigen A (SSA) and immunoglobulin G (IgG). Additionally, MDDST significantly decreased serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17), while enhancing levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), thereby regulating the Th17/Treg immune balance. Further investigations revealed that MDDST treatment induces alterations in gut microbiota composition and elevates SCFA levels in the gut. Subsequent FMT and SCFA intervention experiments demonstrated a downregulation of pSS-related phenotypes. Conclusion: In summary, MDDST demonstrates protective effects against pSS by restoring the balance between Th17 and Treg cells. The therapeutic effects can be partially attributed to its regulation of gut microbiota and SCFAs. Our finding provides a new option for treating pSS.

IntroductionPatients with Primary Sjögren’s syndrome (pSS) are at a higher risk of thyroid disorders than the general population. This retrospective analysis of 202 patients with pSS was conducted to uncover risk factors associated with thyroid involvement and to create a predictive model for this condition.MethodsWe analyzed 202 patients with pSS from Guang’anmen Hospital, China Academy of Chinese Medical Sciences, with 105 cases of thyroid involvement and 97 without. The Least Absolute Shrinkage and Selection Operator method was used to identify key variables for our risk model. These variables were then subjected to multivariate logistic regression to develop the model. The accuracy of the model was assessed through the C-index, receiver operating characteristic curves, calibration plots, and decision curve analysis, with internal validation via bootstrapping.ResultsHigh-sensitivity C-reactive protein (HCRP), pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and aspartate aminotransferase (AST) were incorporated into the nomogram. The model showed robust discrimination and calibration abilities. Decision curve analysis indicated the clinical utility of our nomogram in intervening on the probability thresholds of thyroid disease.ConclusionBy integrating HCRP, pulmonary disease, pharyngeal dryness, forgetfulness, night sweats, hyperuricemia, nasal dryness, anxiety, Ro52, and AST, our thyroid risk nomogram can predict the risk of thyroid involvement in patients with pSS, aiding in more informed treatment strategies.

Background: Primary Sjögren's syndrome (pSS) stands as a chronic autoimmune disease characterized by an elusive pathogenesis. The synergy of single-cell RNA sequencing and Mendelian randomization (MR) analysis provides an opportunity to comprehensively unravel the contributory role of monocytes/macrophages in the intricate pathogenesis of pSS. Methods: Differentially expressed genes (DEGs) of various types of immune cells were analyzed after annotating single-cell RNA sequencing (scRNA-seq) data. MR analysis of expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) was conducted to search for key pathogenic genes and proteins. Cellular localization of pathogenic genes was performed based on scRNA-seq data. Variations in signaling pathways between immune cells were further analyzed. Results: A total of 1434 significant DEGs were identified. Among these, 60 genes exhibited strong relevance to the occurrence of pSS, of which 32 genes differentially expressed in monocytes/macrophages. CTSS was found to be a significant risk protein with a p-value of 0.001 and an odds ratio of 1.384 (1.147–1.669), showing pronounced expression in monocytes/macrophages. Furthermore, monocytes/macrophages displayed heightened expression levels of MXD1, AMPD2, TNFSF10, FTL, UBXN11, CSF3R, and LILRA5. The analysis of intercellular signaling revealed increased signal intensity in both incoming and outgoing signals in monocytes/macrophages. The signaling interactions between monocytes/macrophages, B cells, and T cells exhibited varying degrees of deviation. Conclusions: This study highlights the significant involvement of monocytes/macrophages in the pathogenesis of pSS, as evidenced by MR analysis and scRNA-seq analysis. This suggests monocytes/macrophages as a focal point for pathogenesis research and potential therapeutic targeting in pSS.

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.

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]