Search Results (574)

Anti-Ku antibodies are rare autoantibodies associated with connective tissue diseases (CTDs), but their clinical significance remains poorly understood due to limited studies. Semi-quantitative immunodot assays yield positive, negative, or borderline results, with the clinical relevance of borderline findings remaining unclear. The purpose of this study is to characterize the clinical spectrum of anti-Ku-positive patients and evaluate the clinical significance of anti-Ku-borderline results in CTD management. A retrospective cohort study was conducted at Hôpital Erasme, including all patients with anti-Ku-positive or borderline results, over a 10-year period. Clinical and biological data were collected from medical records and analyzed for disease associations, organ involvement, and outcomes. Among 47 anti-Ku-positive patients, systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) were the most common diagnoses. Interstitial lung disease (ILD) occurred in 23.4% and renal involvement in 12.8% of patients. Cytopenia was significantly associated with glomerulonephritis. Organ damage, particularly pulmonary and renal involvement, correlated with increased mortality. In the borderline group (n = 33), SLE and SS remained the predominant diagnoses. During follow-up, three patients died (all with isolated ILD without associated CTD), one required chronic dialysis, and one underwent lung transplantation. ILD was present in 7/22 (31.8%) borderline patients, and renal involvement in 7/32 (21.9%). This study demonstrates significant associations between anti-Ku antibodies and organ damage, with increased mortality risk. The high prevalence of pulmonary and renal involvement in anti-Ku-borderline patients suggests that these results carry substantial clinical significance and should prompt comprehensive CTD evaluation. These findings support treating borderline anti-Ku results with the same clinical vigilance as positive results, given their similar association with severe organ involvement and adverse outcomes. Full article

Background: Anti-synthetase Syndrome (ASyS) is an idiopathic inflammatory myopathy characterized by muscle weakness and inflammatory infiltrates in muscles. Sjogren’s disease (SD) is an autoimmune condition primarily affecting exocrine glands. Both these conditions may present lung involvement. We describe a female patient with anti-synthetase/SD overlap syndrome and review the literature to identify published cases describing this overlap, aiming to better define its clinical, radiological, and serological features. Methods: The case description was based on a retrospective collection of clinical, laboratory, and imaging data related to the patient’s diagnostic process and clinical course. Data were anonymized and handled in accordance with the competent territorial Ethics Committee. A literature review was performed using the MEDLINE and Scopus databases by combining the keywords “Anti-Synthetase syndrome”, “Sjögren disease”, “Sjögren syndrome”, “Myositis”, and “Interstitial lung disease” (ILD). Published cases were selected if they met the 2016 EULAR/ACR criteria for SD and at least one of the currently proposed classification criteria for ASyS. Results: The described case concerns a 68-year-old woman with rapidly progressive ILD. The diagnosis of anti-synthetase/SD overlap syndrome was based on clinical, serological (anti-Ro52 and anti-PL7 antibodies), histological, and radiological findings. Despite immunosuppressive and antifibrotic treatment, the clinical course worsened, leading to a poor outcome. In addition, six relevant cases were identified in the literature. Clinical presentations, autoantibody profiles, radiological findings, and outcomes were highly heterogeneous. Among the reported cases, no standardized treatment protocols were adopted, reflecting the lack of consensus in managing this rare condition. Conclusions: In anti-synthetase/SD overlap syndrome, ILD may follow a rapidly progressive course. Early recognition can be challenging, especially in the absence of muscular involvement. This case-based review highlights the need for more standardized approaches to the diagnosis and management of this rare and complex overlap syndrome. Full article

Background: Polygenic risk scores (PRS) have emerged as promising tools for disease risk stratification. However, their validity across different populations remains unclear, particularly for autoimmune diseases, where environmental factors may play crucial roles. Methods: We calculated the population-level PRS for Sjögren’s syndrome using seven validated genetic variants (PGS001308) and allele frequency data from the 1000 Genomes Project Phase 3 for five European populations (CEU, TSI, FIN, GBR, and IBS). PRS values were correlated with published prevalence estimates from a systematic literature review. Statistical analyses included Pearson’s correlation and sensitivity analyses. Results: PRS values varied across European populations, ranging from 0.317 in the Spanish population to 0.370 in the Northern European population. A non-significant negative trend was observed between population PRS and Sjögren’s syndrome prevalence (r = −0.407, R² = 0.166). Italy showed the lowest genetic risk score (TSI: 0.349) but the highest disease prevalence (58.2 per 100,000), while Northern European populations demonstrated a higher PRS but lower prevalence. Conclusions: No significant correlation was found between genetic risk scores and disease prevalence in this limited sample of five European populations. Larger studies are needed to clarify the relationship between polygenic risk and disease prevalence. Full article

Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include Raynaud’s phenomenon and “mechanic’s hands”. Among antisynthetase antibodies, anti-PL-12 is notably associated with predominant or isolated ILD and may occur in the absence of clinically evident myositis, thereby complicating timely diagnosis. Case Presentation: We are presenting a 45-year-old non-smoking female patient with a prior diagnosis of seronegative rheumatoid arthritis (RA) who developed progressive dyspnea, dry cough, and sicca symptoms. High-resolution computed tomography revealed a nonspecific interstitial pneumonia (NSIP) pattern. Despite normal creatine kinase and lactate dehydrogenase levels, serological work-up revealed positive anti-PL-12 and anti-Ro52 antibodies, supporting a diagnosis of antisynthetase syndrome without myositis, fulfilling the diagnostic criteria for ASyS per Connors and Solomon. Treatment with corticosteroids and cyclophosphamide induced clinical and functional respiratory improvement, while azathioprine was initiated for maintenance. Conclusions: This case underscores the clinical heterogeneity of antisynthetase syndrome and highlights the diagnostic challenge posed by anti-PL-12–associated ILD in the absence of myositis. Importantly, it demonstrates that in patients with pre-existing rheumatologic diagnoses, the emergence of atypical pulmonary manifestations warrants repeat serologic evaluation to assess ASyS and other autoimmune conditions. Early diagnosis and immunosuppressive treatment are essential to optimize outcomes. Full article

Topically applied TH1579 alleviated the psoriatic phenotype in the imiquimod-induced psoriasis mouse model by decreasing CD45⁺, Ly6b⁺, and CD3⁺ cell infiltration and downregulating the expression of the proliferation marker PCNA. Moreover, TH1579 strongly suppressed IL-17 expression in mouse skin, accompanied by reduced infiltration of IL-17-producing γδ-T cells. Furthermore, TH1579 decreased keratinocyte viability and proliferation. Mass spectrometry data analysis revealed the enrichment of proteins associated with nucleotide excision repair and cell cycle regulation. The key cell cycle regulatory protein F-box protein S-phase kinase-associated protein 2 (SKP2) was significantly downregulated, along with the psoriasis-associated proliferation marker WNT5a, identified as a SKP2 downstream target. The downregulation of SKP2 and WNT5a was confirmed in MTH1i-treated mouse skin. Our findings support the topical administration of MTH1i TH1579 as a psoriasis treatment. The therapeutic effects depended on the SKP2/WNT5a pathway, which mediates psoriatic hyperproliferation. This study introduces a conceptually innovative topical treatment for psoriasis patients with mild-to-moderate disease who have limited therapeutic options. Full article

Autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome show pronounced sex disparities in prevalence, severity, and clinical outcomes, with females disproportionately affected. Emerging evidence highlights sex-based differences in immune and inflammatory responses as key contributors to this bias. Genetic factors—including sex chromosomes, skewed X chromosome inactivation, and sex-biased microRNAs—as well as sex hormones and pregnancy modulate gene expression and immune cell function in a sex-specific manner. Additionally, sex hormone-dependent epigenetic modifications influence the transcription of critical immune regulators. These genetic and hormonal factors collectively shape the activation, differentiation, and effector functions of diverse immune cell types. Environmental factors—including infections, gut microbiota, environmental chemicals and pollutants, and lifestyle behaviors such as diet, smoking, UV exposure, alcohol and caffeine intake, physical activity, and circadian rhythms—further modulate immune function and autoimmune disease pathogenesis in a sex-dependent manner. Together, these mechanisms contribute to the heightened risk and distinct clinical features of autoimmunity in females. A deeper understanding of sex-biased immune regulation will facilitate the identification of novel biomarkers, enable patient stratification, and inform the development of sex-specific diagnostic and therapeutic strategies for autoimmune diseases. Full article

Cerebellar ataxias are a group of disorders characterized by clumsy movements because of defective muscle control. In affected individuals, muscular impairment might have an impact on activities like walking, balance, hand coordination, speech, and feeding, as well as eye movements. The development of symptoms typically takes place during the span of adolescence, and it has the potential to cause distress for individuals in many areas of their lives, including professional and interpersonal relationships. Although skeletal muscle is understudied in ataxias, its examination may provide hitherto unexplored details in this family of disorders. Observing muscle involvement can assist in diagnosing conditions where genetic tests alone are inconclusive. Furthermore, it helps determine the stage of progression of a pathology that might otherwise be challenging to assess. In this study, we reviewed the main scientific literature reporting on skeletal muscle examination in autosomal recessive cerebellar ataxias (ARCAs), with a focus on the rare Marinesco–Sjögren syndrome. (MSS). Our aim was to highlight the similarities in muscle alterations observed in ARCA patients while also considering data gathered from preclinical models. Analyzing the similarities among these disorders could enhance our understanding of the unidentified mechanisms underlying the phenotypic evolution of some less common conditions. Full article

Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown benefits in promoting tear secretion and corneal healing. This study evaluated the safety and efficacy of insulin nanoemulsion eye drops (20 IU/mL, three times daily for 30 days) in patients with SjD. Thirty-two patients were randomized in a double-masked design to receive either insulin or placebo drops. Symptoms (assessed by OSDI questionnaire) and objective measures (tear film breakup time, corneal and conjunctival staining, and Schirmer Test) were recorded at baseline, after 4 weeks of treatment, and at a 4-week follow-up. Twenty-three participants completed the study. Both groups showed significant improvement in symptoms and objective signs after treatment (p < 0.05), but no significant differences were found between the insulin and placebo groups. No clinically relevant adverse effects were reported. Insulin nanoemulsion eye drops are safe for SjD patients, but their therapeutic advantage remains unclear. Further studies with larger samples, extended follow-up, and dose adjustments are needed to better understand their potential. Full article

Compelling evidence has demonstrated a bidirectional relationship between Sjögren’s syndrome (SS) and periodontitis (PD). Nevertheless, the underlying mechanisms driving their co-occurrence remain unclear, highlighting the need for finding the hub gene. This study sought to examine the common genes and any connections between SS and PD. Differently expressed genes (DEGs) were analyzed by means of gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) methods. The test and validation sets were used to depict the receiver operating characteristic (ROC) curves. The immune cell infiltration was performed via the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) methodology. The relationships between immune infiltrating cells and the common gene were examined. Ninety-five common genes with similar expression trends were obtained after DEGs analysis, which were enriched in cytokine—cytokine receptor interaction, chemokine signaling pathway, proteasome, intestinal immune network for IgA production, and cytosolic DNA sensing pathway. Thirty-nine common genes were obtained after WGCNA. Sixteen shared genes of DEGs analysis and WGCNA were incorporated into the LASSO model to obtain the unique shared gene, C-C motif chemokine receptor 1 (CCR1), which overexpressed and owned predictable ROC curves in test and validation sets. The examination of immune cell infiltration underscored its crucial roles in the disturbance of immune homeostasis and the emergence of pathogenic circumstances with the simultaneous occurrence of SS and PD. CCR1 overexpresses and serves as a critical pathogenic hub linking SS and PD, which may play a role through immune cell infiltration. Full article

Sjogren’s syndrome is an autoimmune disease that may be triggered by environmental factors. While the impact of perfluoroalkyl substances (PFASs) on the human immune system has been investigated, their specific effect on Sjogren’s syndrome remains unreported. We conducted this study to evaluate the association between PFAS exposure and clinical manifestations of pSS. In total, 136 patients with pSS and 148 healthy controls in the Second Affiliated Hospital of Zhejiang University School of Medicine were investigated. The concentrations of perfluoroundecanoic acid (PFUdA) in the pSS group were statistically significantly higher than those in the healthy control group. Compared to patients without leukopenia and thrombocytopenia, those with the condition had significantly lower concentrations of perfluorononanoic acid (PFNA). The serum levels of PFNA and perfluorodecanoic acid (PFDA) were found to be lower in patients with a high antinuclear antibody (ANA) titer compared to those with a low ANA titer. The serum levels of PFNA were found to be lower in patients who were anti-Sjögren’s syndrome A (anti-SSA)-positive compared to those who were anti-SSA-negative. These results indicate that the levels of serum PFASs may be correlated with the disease activity in pSS patients, and there might be an association between PFASs and the onset of pSS. Full article

Sicca syndrome is a common condition that draws the attention of rheumatologists, and is frequently related to Sjögren’s disease (SjD). This study analyzed 164 patients with sicca syndrome (clinically suspected for SjD) who underwent minor salivary gland biopsy (mSGB). Patients completed the Xerostomia Inventory (XI) and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires to assess Patient-Reported Outcome Measures (PROMs), and biopsies were graded using the Chisholm and Mason system. Patients were classified as seropositive (SSA, SSB, Ro52, Ro60 positive) or seronegative, and also divided into three groups by age. Positive biopsies (60.37%) were more common in older patients (61–80) and associated with confirmed SjD, more severe xerostomia, and stronger lymphocytic infiltrates. Among these, 37.37% were seropositive, showing higher disease activity, hypergammaglobulinemia, and elevated IgG. Seronegative patients had a heavier symptom burden, confirmed by the PROMs, and more fibrosis and fatty replacement in biopsies. Age-stratified analysis showed younger patients (18–40) were more affected by ocular dryness, while older patients had worse xerostomia and more severe histological and ultrasound changes. Younger individuals had higher IgG/IgA, more anemia, and reduced C3. Hydroxychloroquine was used more in younger and seropositive groups; older patients used more topical therapies. These results highlight mSGB’s diagnostic value, especially in seronegative cases, and stress the importance of combining clinical, histological, imaging, and patient-reported outcomes for optimal care. Full article

Pulmonary arterial hypertension (PAH) is a severe complication associated with connective tissue diseases (CTDs), which is characterized by a significant influence on the patient’s prognosis and mortality. The prevalence of PAH varies depending on the type of CTD. Still, it is highly prevalent in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and primary Sjögren’s syndrome (pSS). Identifying rheumatic disease-specific risk factors is crucial for early diagnosis and intervention. Risk factors for PAH development include specific sociological factors (related to race, gender, and age), clinical features (particularly severe Raynaud’s phenomenon and multiple telangiectasias), cardiological factors (pericarditis and left heart disease), biochemical factors (elevated NT-proBNP and decreased HDL-cholesterol), serological factors (presence of ANA, e.g., anti-U1-RNP or SSA, and antiphospholipid antibodies), and pulmonary factors (interstitial lung disease and decreased DLCO or DLCO/alveolar volume ratio < 70%, FVC/DLCO > 1.6). The analysis of risk factors can be the most useful during the selection of patients at high risk of PAH development. The initial diagnosis of PAH is usually based on transthoracic echocardiography (TTE) and is finally confirmed by right heart catheterization (RHC). Targeted therapies can improve outcomes and include endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase inhibitors, and tailored immunosuppressive treatments. Effective management strategies require a multidisciplinary approach involving rheumatologists, cardiologists, and pulmonologists. The risk stratification and individualized treatment strategies can enhance survival and quality of life in patients with PAH-CTD. Full article

Background/Objectives: This study investigates the macular microvasculature in a large cohort of primary Sjögren’s disease (SjD) patients using optical coherence tomography angiography (OCTA), focusing on how disease duration, activity, and hydroxychloroquine (HCQ) treatment influence retinal microcirculation. Methods: A total of 106 eyes (53 SjD patients) and 70 eyes (35 age- and gender-matched healthy controls (HCs)) were examined. The vessel area density (VAD, %) and foveal avascular zone (FAZ, mm2) were measured in three retinal layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP), respectively, in three peri-macular circular sectors (c1, c2, c3) each. Results: The VAD was significantly lower in c1 of the DCP in SjD compared to HCs (29.14 ± 7.07 vs. 31.78 ± 9.55, p = 0.038). The FAZ was significantly larger in SjD in both SVP (0.41 ± 0.13 vs. 0.34, 0.11, p < 0.001; Cohen’s |d| = 0.55) and DCP (0.45 ± 0.15 vs. 0.4 ± 0.14, p = 0.014; Cohen’s |d| ± 0.38). Significant correlations were observed between the FAZ size and reductions in the VAD in the SVP and DCP (p = 0.010, Cohen’s |d| = 0.2; p < 0.001, Cohen’s |d| ± 0.26) and across all layers combined (p = 0.019, Cohen’s |d| = −0.18). Conclusions: There was a negative correlation between the VAD in the DCP and disease duration (ρ = −0.28, p = 0.040). No significant correlation was identified between the duration of HCQ intake and the VAD or FAZ. Our findings indicate microvascular alterations in the DCP of SjD, characterized by a reduced VAD and an enlarged FAZ, which may be attributable to inflammatory or arteriosclerotic factors. OCTA may prove to be a valuable tool for the stratification of vascular risk in SjD. Full article

Sjögren’s Disease (SjD), Rheumatoid Arthritis (RA), and Systemic Lupus Erythematosus (SLE) are autoimmune diseases with overlapping genetic features, yet the etiologies of these diseases are poorly understood. Using these rheumatic diseases as an example of proof of concept, our aim was to develop a tool that simplifies analysis of gene–disease associations applicable to any disease and to perform comparisons. This tool is meant to provide insights into associated gene symbols and gene expression data to identify candidate biomarkers in common among these diseases. The Diseasesv2.0 and GTExv8 databases were utilized for data collection, providing searchable disease names, affiliated gene symbols, confidence scores (ranging from 0 to 5, with 5 being the most confident), and gene expression across the panel of 54 tissue types present in GTExv8. Data infrastructure was established on a Postgres database using Plotlyv5.17.0 and Streamlitv1.27.2 Python packages. The resulting database was used to investigate the genetic associations among SjD, RA, and SLE, including confidence scores from 2.50 to 5.00. STRINGv12 analysis determined significant pathways (FDR < 0.05). Analysis using our tool revealed the following refined gene associations for each disease: SjD based on ‘Sjogren’ search term (n = 12 genes), RA (n = 231 genes), and SLE (n = 137 genes). We found seven genes in common, namely, CD4, CD8A, IL6, IL17A, TNFS13B, TNF, and TRIM21. With the exception of IL17A, these genes were expressed in tissue types known or suggested to be affected by SjD. STRINGv12 determined significant KEGG pathways involving interleukin signaling, cytokine signaling, and the immune system. We developed a tool that simplifies the data mining process, allowing users to search for diseases of interest and view common gene associations and gene expression. Some of the genes identified through our tool may be further explored to better understand SjD pathogenesis and systemic impact. Full article

Sjögren’s disease is multi-system autoimmune disease characterized by dryness of mucosal surfaces, fatigue, and pain. Heterogeneity among patients is a major obstacle for timely diagnosis, management of patients, and clinical trial design. Strategies for patient stratification are therefore desperately needed. In this review, we aimed to summarize current stratification approaches. Two major approaches for patient stratification are currently used. The first one is based on patient-reported symptoms and the subsequent analysis of the clinical and biological characteristics defining the identified clusters. The second strategy is based on the molecular stratification of patients, followed by the analysis of clinical characteristics along with other biological data. The combination of different approaches holds great potential to improve the recognition of patient subgroups and the development of tailored therapies. The current literature suggests that three to four subgroups of patients with SjD exist. Whether these subgroups represent disease stages or disease endotypes is still a matter of debate and will be a topic of future research. Full article