Clinical and experimental rheumatology最新文献

Objectives: Quality of life (QoL) in patients with Sjögren's disease (SjD) is a critical area of research that demands attention due to the impact of SjD on patients' lives. This study utilised bibliometric methods, aiming to comprehensively explore the research content and hotspots in the field of QoL in patients with SjD.

Methods: The literature data source for this study was the Web of Science Core Collection. CiteSpace and VOSviewer were used to analyse publications in relation to authors, countries, institutions, journals, references, and keywords.

Results: The study focused on literature that addressed QoL in SjD patients, involving a total of 922 authors and 336 articles published across 151 journals. The study revealed that the number of publications in this field has remained relatively low, exhibiting a stable yet gradual upward trend, with no evidence of explosive growth. Key journals in this field include the Journal of Annals of the Rheumatic Diseases, Rheumatology (Oxford), Clinical and Experimental Rheumatology, and the Journal of Arthritis & Rheumatology. Asghar Bowman Simon J is the most prolific author in the field (21 publications), and England and the University Hospitals Birmingham NHS Foundation Trust and University of Groningen have the most publications. The most high-frequency keywords are "Sjögren's syndrome", "quality of life," "fatigue", "xerostomia", "depression", "sexual dysfunction" and "xerophthalmia".

Conclusions: This study represents a bibliometric analysis focusing on QoL in patients with SjD. It underscores the need for more extensive and systematic research in this area, emphasising the importance of a multidisciplinary approach. Despite advancements in medical research for SjD, there is a crucial need to focus on QoL to enhance patient satisfaction and overall well-being. The findings advocate for more personalised treatment plans and a better understanding of the psychosocial needs of patients with SjD to improve their quality of life.

Objectives: Current evidence on how training influences the reliability of salivary gland ultrasound (SGUS) image scoring is scarce, particularly in the context of Sjögren's disease (SjD). This study aimed to address this gap by evaluating the effect of a structured training workshop on inter-observer reliability in SGUS scoring among clinicians assessing patients with SjD.

Methods: 25 healthcare professionals from 10 countries, with varying SGUS expertise participated. In random order, SGUS images of 20 suspected SjD patients were assessed before and after the workshop. Images included grey-scale (GS) and colour Doppler (CD) scans of the submandibular and parotid glands and were scored using the OMERACT GS and CD scoring systems. Intraclass correlation coefficients (ICC) assessed overall inter-observer reliability, and participant vs. SGUS-expert reliability (gold standard-participant agreement). Analyses were stratified by SGUS experience (none vs. ≥1 year).

Results: The inter-observer reliability ICC for the total OMERACT score was 0.68 pre-workshop vs. 0.79 post-workshop for GS, and 0.73 pre-workshop vs. 0.72 post-workshop for CD. Training significantly improved the gold standard-participant ICC GS (0.06±0.12, p=0.020), particularly for the submandibular glands, while the CD ICC showed a minor, non-significant improvement (0.03±0.09, p=0.129). Inexperienced participants (n=11) showed significant ICC improvement for the total GS OMERACT score (0.13±0.13, p=0.012), whereas experienced participants (n=14) showed a negligible change (0.01±0.09, p=0.624). No significant differences were observed for CD scoring.

Conclusions: A training workshop was associated with improvements for inter-observer reliability for GS SGUS, particularly in submandibular gland assessment and among inexperienced participants. The effects on CD scoring were minimal.

Objectives: This study aimed to evaluate the association between visceral adipose tissue (VAT) levels and inflammation, disease activity, and functional impairment in women with primary Sjögren's Disease (SjD).

Methods: We included 100 female patients with SjD from a tertiary care clinic who met the ACR/EULAR 2016 classification criteria. Disease activity was assessed using the ESSDAI and ESSPRI scores, while cumulative damage was evaluated by the SSDDI. Inflammatory markers, synovitis (via ultrasound), and functional disability using the HAQ were measured. Body composition, including VAT, was analysed using dual-energy X-ray absorptiometry. Handgrip strength and physical activity (Baecke questionnaire) were also assessed. Patients were categorised into VAT tertiles, and comparisons were made to healthy controls. Correlations between VAT, disease activity, and synovitis were analysed using multiple regression models.

Results: The patients had a mean age of 50.5±9.3 years, BMI of 28.2±5.6 kg/m², and median disease duration of 8 years. The highest VAT tertile was associated with a higher prevalence of synovitis (75.7% vs. 51.5%; p=0.041), lower handgrip strength (p=0.025), and higher HAQ scores (p<0.001). VAT mass was significantly correlated with obesity (p<0.001), functional disability (p=0.002), and ESSPRI (p=0.01). Postmenopausal patients had significantly higher VAT levels than premenopausal patients (p=0.005). There were no significant correlations between VAT and inflammation.

Conclusions: Elevated VAT levels in SjD are associated with increased disease activity, a higher prevalence of synovitis, and greater functional disability, suggesting that VAT may contribute to the functional impairment observed in SjD.

Objectives: Sjögren's disease (SjD) is a systemic autoimmune disorder characterised by chronic lymphocytic inflammation of the salivary and lacrimal glands, leading to progressive dysfunction and tissue damage. Salivary gland ultrasonography (SGUS) enables standardised, semiquantitative evaluation of glandular structure. While grey-scale (B-mode) scoring systems such as De Vita et al. and OMERACT are widely used, the recently validated colour Doppler (CD) OMERACT scoring system allows assessment of glandular vascularisation. However, its relationship with structural imaging and clinical disease activity remains uncertain. The aim of the study is to assess the correlation between CD ultrasonography and established B-mode scores, and to explore the clinical significance of vascular assessment in patients with SjD.

Methods: Sixty-three consecutive patients fulfilling the 2016 ACR/EULAR criteria for SjD underwent standardised SGUS of parotid and submandibular glands using De Vita et al., B-mode OMERACT, and CD OMERACT semiquantitative scores (0-3). Clinical, serological, and disease activity parameters were recorded and correlated using Spearman's rank coefficient.

Results: Most patients exhibited moderate to severe B-mode alterations, while higher CD grades (2-3) were less frequent. CD OMERACT scores correlated moderately with De Vita et al. (ρ=0.44, p<0.001), B-mode OMERACT (ρ=0.48, p<0.001), and glandular ESSDAI (ρ=0.43, p<0.001). SjD-related lymphoma showed weak but significant correlation with CD OMERACT and moderate correlation with both B-mode scores.

Conclusions: Colour Doppler ultrasonography reflects inflammatory vascular changes paralleling structural and clinical disease activity in SjD. Although it does not yet provide independent diagnostic value, further studies are needed to define the role of Colour Doppler as a complementary tool in salivary gland ultrasonography for assessing glandular inflammation and lymphoproliferative risk.

Objectives: Sjögren's disease (SjD) is a highly heterogeneous autoimmune disease with substantial challenges in early diagnosis and therapeutic intervention. We developed an integrated approach combining machine learning algorithms, SHAP interpretable modelling, molecular docking, and single-cell analysis to facilitate early diagnosis and treatment of SjD.

Methods: Transcriptomic data and 12 machine learning algorithms were employed to identify diagnostic signature genes. SHAP (Shapley Additive exPlanations) analysis further prioritised hub genes, followed by functional annotation using CIBERSORT, GSVA, and GSEA. Validation was performed using clinical cohorts, single-cell RNA sequencing (scRNA-seq), and molecular docking.

Results: The training cohort comprised 382 samples (61 healthy controls, 321 SjD patients) and 10,015 genes. Machine learning and SHAP analysis identified three hub genes (CD248, MMP28, SLC16A10), validated in external datasets with significant differential expression (p<0.05) and robust diagnostic performance (AUC >0.7). Immune infiltration analysis revealed positive correlations between CD248/SLC16A10 and naive CD4+ T cells (p<0.05), and between SLC16A10/MMP28 and memory resting CD4+ T cells (p<0.05). Single-cell profiling localised CD248 predominantly in naive CD4+ T cells, while SLC16A10 and MMP28 were expressed in both naive and memory CD4+ T cells subsets. Molecular docking demonstrated stable targeting of CD248, MMP28, and SLC16A10 by azathioprine, leflunomide, methotrexate, hydroxychloroquine, iguratimod, pilocarpine, and cevimeline.

Conclusions: Our bioinformatic study identifies CD248, MMP28 and SLC16A10 as candidate biomarkers and therapeutic targets for SjD, with their dysregulation specifically enriched in CD4+ T cell subsets, unveiling a previously underappreciated mechanism in SjD pathogenesis. naive and memory CD4+ T cells emerge as key contributors to inflammatory cascades, with azathioprine, leflunomide, methotrexate, hydroxychloroquine, iguratimod, pilocarpine, and cevimeline predicted to bind potently to these targets. This integrative multi-omics framework, combining machine learning, SHAP, and molecular docking, presents a promising approach for autoimmune disease diagnostics and early therapeutic intervention, although future experimental validation is essential to confirm its translational potential.

Sjögren's disease represents a complex systemic autoimmune disorder mainly driven by T and B lymphocytic infiltration of exocrine gland, activation of different signalling pathways and systemic cytokine production. These interacting pathogenic mechanisms may differently contribute to characterise highly variable phenotypic expression of the disease, ranging from an asymptomatic, indolent course with only glandular involvement to several extra-glandular systemic manifestations. Moreover, approximately 5-10% of patients develop lymphoproliferative disease, with an overall risk reported to be up to 48 times higher in comparison to healthy population. Due to the substantial clinical heterogeneity of the disease, in recent years, research focused to investigate biomarkers able to identify distinct subtypes of Sjögren's disease, facilitate earlier patient recognition and homogenise patient subgroups in clinical trials aiming to develop tailored therapies. Surely, a more detailed understanding of pathogenetic mechanisms and recognition of different disease phenotypes may facilitate earlier diagnosis, enable recognition of patient clusters and suggest novel therapeutic modalities to address the unmet needs of the disease in the upcoming years. In this review, following the others of this series, we will update the most recent literature on Sjögren's disease focusing in particular on new insights into clinical stratification, imaging techniques and targeted therapeutic advances.

Objectives: To develop and validate a machine-learning (ML) model that flags primary Sjögren's disease (pSjD) patients at high risk of depressive symptoms for earlier clinical attention.

Methods: We retrospectively studied 147 pSjD patients (Nanjing First Hospital, 2019-2022). Depressive symptoms were screened with Patient Health Questionnaire-9 (PHQ-9); PHQ-9 ≥5 was the primary endpoint. Missing data were handled by multiple imputation. Data were split 70/30 for training/testing. After univariate screening and LASSO selection, eight ML algorithms (e.g., logistic regression, support vector machine (SVM), tree/boosting methods) were trained with stratified 10-fold cross-validation. Performance was summarised by AUROC/AUPRC, accuracy, precision/recall, Brier score, and calibration; SHAP provided model explainability.

Results: Four routinely available predictors were retained: fatigue frequency, sleep duration, lymphocyte count, and anti-Ro52 status. Across repeated cross-validation, SVM showed the best overall discrimination (mean AUROC≈0.90) with strong precision and accuracy. In the held-out test set, SVM maintained high performance (AUROC=0.929; AUPRC=0.959; Brier=0.106). SHAP confirmed predictor importance, indicating higher risk with shorter sleep, lower lymphocyte counts, greater fatigue frequency, and anti-Ro52 positivity.

Conclusions: This study presents the first ML-based model for predicting depressive symptoms in pSjD patients, highlighting the significance of immuno-inflammatory and clinical factors in depression pathogenesis. The SVM model offers a robust, non-invasive tool for early identification of high-risk individuals, enabling timely and personalised interventions. However, this single-centre, retrospective design with a modest sample limits generalisability; therefore, independent multi-centre validation is required before clinical use.

Objectives: To systematically review the prevalence, risk and associated factors of organ damage in Sjögren's disease (SjD) and to assess its impact on quality of life and long-term outcomes.

Methods: A systematic search of PubMed (2005-2025) identified studies assessing damage accrual in SjD. Longitudinal and cross-sectional studies enrolling patients fulfilling the 2002 AECG and/or 2016 ACR/EULAR classification criteria were included. Damage was defined using validated indices, the Sjögren's Syndrome Damage Index (SSDI) or the Sjögren's Syndrome Disease Damage Index (SSDDI), or through conceptual definitions of irreversible disease attributable injury. The lymphoma domain was excluded. Study selection followed PRISMA guidelines, and predefined PICO frameworks guided data extraction.

Results: Twenty-three studies were included. Glandular damage was reported in 25-86% of patients, while systemic damage affected 9-73%. Older age, longer disease duration, higher baseline ESSDAI, hypergammaglobulinaemia, hypocomplementaemia, and absence of hydroxychloroquine therapy were the most consistent predictors of damage accrual. Pulmonary and renal involvement were associated with increased mortality and hospitalisation rates. Cumulative SSDDI scores correlated with reduced health-related quality of life (HRQoL).

Conclusions: Organ damage in SjD is common nd progressive, reflecting sustained immunologic activity and agingrelated vulnerability. Damage burden predicts poorer outcomes and diminished HRQoL. Standardisation of damage definitions and assessment tools is essential to improve comparability across studies and to guide preventive therapeutic strategies.

Objectives: To investigate the effect of treatment in a series of patients with Sjögren's disease (SjD) associated interstitial lung disease (ILD).

Methods: Twenty-four primary SjD-ILD patients, followed-up from October 2022 to June 2025 were included in the study. Based on clinical judgement, 12 received treatment for ILD, while 12 did not, following a "watch-and-wait" policy. Participants were evaluated in 2 time points with an interval of 24±6 months. ILD was diagnosed by HRCT according to Fleischner Society definitions, performed at baseline due to respiratory symptoms and/or abnormal pulmonary function tests. Spirometry and diffusing capacity for carbon monoxide (DLCO) were performed at both visits. Progression of ILD was defined as absolute decline of predicted forced vital capacity (FVC) ≥5%.

Results: The treatment regimens of 12 SjD-ILD patients who received treatment included rituximab, mycophenolate mofetil, azathioprine and tocilizumab. The treated group displayed higher extent of ILD on HRCT at baseline visit (median: 20% vs. 10%, p=0.006), more frequently findings of small airways disease on HRCT (58% vs. 8%, p=0.027) and tended to present lower FVC (mean: 81.3% vs. 96.7%, p=0.086) compared to the untreated. FVC and DLCO remained stable between baseline and follow-up visit in both groups. However, the change in DLCO between the two visits was worse in the treated than untreated patients (mean: -11.2% vs. 4.8%, p=0.003). The number of SjD-ILD patients presenting progression of ILD did not differ between the two groups (25% vs. 33%, p=0.999).

Conclusions: SjD-ILD clinical course is variable, with the most aggressive form to be controlled by immunosuppressive treatment.