Primary Sjogren's Syndrome Research Articles

Sjögren's syndrome and psoriasis: a two-sample Mendelian randomization study.

Primary Sjögren's Syndrome (PSS) and psoriasis are frequently observed to co-occur in clinical settings. However, the causal associations and underlying mechanisms between PSS and psoriasis remain poorly defined. In this study, we conducted bidirectional MR analysis to explore the causal relationship between PSS and psoriasis using four MR methods: inversevariance weighted, MR-Egger regression, weighted median, and weighted mode. Sensitivity analyses were carried out, employing different models and testing methods for comparison to assess the influence of heterogeneity and pleiotropy on our findings and to confirm the robustness of these results. We primarily employed the Inverse Variance Weighting (IVW) method for our analysis. A p-value of less than 0.05 indicates a significant causal relationship, while a p-value greater than 0.05 suggests the absence of such a relationship. The IVW analysis confirmed a causal relationship between psoriasis and primary Sjögren's syndrome (PSS) (OR: 3.149E-10, 95% CI 1.114E-18-0.089, P = 0.028), with the weighted median yielding similar results. Conversely, there was no causal association found between PSS and the risk of developing psoriasis (OR: 1.000, 95% CI 0.999-1.000, P = 0.328). This study reveals a causal relationship between primary Sjögren's syndrome (PSS) and psoriasis, demonstrating that psoriasis increases the risk of developing PSS, while the reverse is not true. This potential causal link offers new insights into the etiology of both PSS and psoriasis.

The Value of Lacrimal Gland Ultrasonography and Shear Wave Elastography in the Evaluation of Primary Sjögren's Syndrome: A Cross-Sectional Study.

This study evaluates the effectiveness of lacrimal gland ultrasonography (LGUS) and shear wave elastography (SWE) in distinguishing primary Sjögren's syndrome (PSS) patients from healthy controls and examines their role in assessing disease activity and prognosis. A total of 35 PSS patients and 23 age- and gender-matched healthy controls were included. LGUS was used to grade lacrimal gland structure, while SWE assessed gland elasticity. Disease activity and prognosis were evaluated using european league against rheumatism sjögren's syndrome disease activity index (ESSDAI)and serologic markers. Compared with healthy controls, LGUS, Emean, and shear wave velocity (SWV) were significantly higher in PSS patients. The optimal cut-off value of LGUS for diagnosis of PSS was 2 (area under the curve [AUC]: 0.832, sensitivity: 80.0%, specificity: 69.6%), the optimal thresholds for diagnosis of PSS using Emean and SWV values are 9.4 kPa (AUC: 0.768, sensitivity: 65.7%, specificity: 82.6%) and 1.7 m/s (AUC: 0.823, sensitivity: 71.4%, specificity: 91.3%), respectively. There are statistical differences in Emean and SWV between subgroups based on european league against rheumatism sjögren's syndrome disease activity index (ESSDAI); there are statistical differences in LGUS, Emean, and SWV between subgroups based on IgG levels and complement titers. LGUS and SWE are accurate, noninvasive diagnostic tools for PSS and may serve as indicators of disease activity and prognosis.

Inhibiting miR-155-5p promotes proliferation of human submandibular gland epithelial cells in primary Sjogren's syndrome by negatively regulating the PI3K/AKT signaling pathway via PIK3R1.

To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS). Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay. ELISA and RT-PCR were used to detect the expressions of inflammatory cytokines and miR-155-5p mRNA in the cells; Western blotting was performed to detect the expressions of proteins in the PI3K/AKT signaling pathway. Dual luciferase assay showed that miR-155-5p targets the PI3K/AKT pathway via PIK3R1 mRNA. The HSGEC model of pSS showed significantly decreased cell viability, cell clone formation ability and expressions IL-10 and IL-4 and increased cell apoptosis, cell percentage in G2 phase, expressions of TNF‑α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-Akt/AKT ratio, and PIK3R1 protein expression. Treatment of the cell models with miR-155 inhibitor significantly increased the cell viability, G1 phase cell percentage, colony formation ability, and expressions of IL-10 and IL-4 levels, and obviously reduced cell apoptosis rate, G2 phase cell percentage, expressions of TNF-α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-AKT/AKT ratio, and PIK3R1 protein expression. In HSGEC model of pSS, inhibition of miR-155-5p can promote cell proliferation and reduced cell apoptosis by targeting PI3K1 mRNA to negatively regulate the overexpression of PI3K/AKT signaling pathway.

Serology and histology in Sjögren's syndrome diagnosis: a retrospective accuracy study.

Sjögren's syndrome (SS) presents complex diagnostic challenges due to its multi-organ involvement, often leading to misdiagnosis, which can result in unnecessary treatments, elevated healthcare costs, and significant impacts on patient quality of life. Accurate diagnosis is therefore critical, utilising ACR/EULAR criteria that include both labial minor salivary gland (LMSG) biopsy and anti-SSA antibodies. This retrospective study analysed medical records of 87 adults suspected of primary SS, who underwent both anti-SSA serology and LMSG biopsy. We evaluated the diagnostic accuracy of these tests under existing ACR/EULAR criteria and a newly proposed 'modified ACR/EULAR criteria-ClinDx'. Statistical analysis included Pearson's chi-square test for the association between test results and disease status and receiver operating characteristic (ROC) curves to assess the sensitivity and specificity of the diagnostic models. Utilising ACR/EULAR criteria, 40 patients were diagnosed with SS, while 47 were categorised as non-diseased. The ClinDx criteria application resulted in 32 SS diagnoses and 55 non-diseased classifications, highlighting discrepancies in patients with low anti-SSA titers (< 200 MFU). Statistical analysis confirmed a significant association (p < 0.001) between test results and disease status, indicating the robustness of the modified criteria in enhancing diagnostic accuracy. This study underscores the utility of integrating serological tests and histological biopsies in diagnosing SS. While anti-SSA antibodies provide a good preliminary screening tool, the specificity of LMSG biopsies is indispensable. Refining both serological and histological assessments per ClinDx criteria can improve diagnostic accuracy, aiding in better management of SS and reducing healthcare burdens.

Screening for presence of primary Sjogren's syndrome in patients with autoimmune thyroid diseases.

Autoimmune thyroid disorders (AITD) are the most common autoimmune human disorders as the thyroid gland is a main target for autoimmunity. The association between rheumatologic and thyroid disorders has long been known, the most common being the association with rheumatoid arthritis. Our study was conducted to screen for the presence of symptoms, signs, and immune markers suggesting the presence of Sjogren's syndrome among patients with autoimmune thyroid disorders. Eighty AITD patients (46 patients with Hashimoto's thyroiditis and 34 patients with Graves' disease) were included in the study and 40 healthy subjects matched age and sex as a control group. The two groups were compared according to 2002 the American-European Consensus Group (AECG) criteria for diagnosis of primary Sjogren's syndrome. 12.5% of AITD patients (n = 10 patients) were diagnosed with Sjogren's syndrome (AITD-SS). Eight out of ten of AITD-SS had Hashimoto's disease while only two had Grave's disease. Anti-Ro was detected in serum of seven patients of the AITD patients with Sjogren syndrome while anti-La was detected in serum of eight patients. The most independent predictors of Sjogren's syndrome in AITD patients are anti-La, ESR, and salivary gland sonographic change. Sjogren's syndrome has been found in patients with AITD, and also patients with AITD have symptoms that mimic sicca disease despite not fulfilling the criteria for diagnosis.

Gut Microbiota on Anxiety and Depression in Primary Sjogren's Syndrome: A Novel Insight

Gut Microbiota on Anxiety and Depression in Primary Sjogren's Syndrome: A Novel Insight

Clinical, Histopathological, and Serological Comparisons between Primary and Secondary Sjogren's Syndrome

Clinical, Histopathological, and Serological Comparisons between Primary and Secondary Sjogren's Syndrome

Atypical initial presentations of Sjogren's syndrome: a case series.

Primary Sjogren's syndrome (pSS) typically presents with Sicca symptoms xerostomia and xeropthalmia. This study highlights atypical presentations of Primary Sjogren's syndrome posing diagnostic and therapeutic challenges. Four female patients (median age 30 years, IQR = 15.5) with atypical pSS features, confirmed by positive Anti-Ro antibodies and negative lupus or rheumatoid arthritis tests, were treated between February and August 2023. PSS presented as erythema nodosum, soft tissue swelling with medium-vessel vasculitis, palpable purpura, and severe thrombocytopenia in these cases prior to Sicca symptoms. Initial treatment included steroids and hydroxychloroquine. Azathioprine, Methotrexate, and Cyclophosphamide were added as steroid-sparing agents. Three patients achieved remission. One patient with co-existing pulmonary tuberculosis (TB) died. Atypical features can occur in SS, requiring vigilance for diagnosis and individualised treatment. Our series demonstrates the diverse atypical clinical features of Sjogren's syndrome, encompassing radiologic, histopathologic, laboratory abnormalities, and treatment guidelines, expanding the known spectrum of disease presentation and management.

EZH2 promotes B-cell autoimmunity in primary Sjogren's syndrome via METTL3-mediated m6A modification

ObjectiveEnhancer of zeste homologue 2 (EZH2) plays an important role in promoting B-cell activation and differentiation. This study aimed to elucidate the role of EZH2 in the B-cell autoimmune response in primary Sjögren's syndrome (pSS) and to explore the therapeutic potential of inhibiting EZH2 in pSS. MethodsSingle-cell RNA sequencing analysis of B cells in peripheral blood from pSS patients was conducted to identify abnormal expression of EZH2 and METTL3 in B-cell subsets. The levels of EZH2 were further validated across multiple B-cell subsets and the salivary glands (SGs) of pSS patients, as well as three different mouse models of Sjögren's syndrome (SS). Correlation analyses were performed to explore the relationship between the expression of EZH2 and clinical features of pSS patients. Following EZH2 inhibition, SS-like signs and antibody production were assessed in an experimental Sjögren syndrome (ESS) mouse model. RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) data post-EZH2 inhibition were bioinformatically analyzed to identify the EZH2 targets in pSS. ChIP-qPCR was performed to validate the binding of H3K27me3 to the CDKN1A promoter. Flow cytometric apoptosis analysis and Carboxy Fluorescein Succinimidyl Ester (CFSE) assay were used to assess the impact of an EZH2 inhibitor on B-cell apoptosis and proliferation. Additionally, METTL3 expression and its correlation with disease activity were analyzed in pSS patients. EZH2 expression was examined after METTL3 knockdown. METTL3-RNA immunoprecipitation (RIP) and actinomycin D assays were conducted to confirm the direct binding of METTL3 to EZH2 mRNA and its impact on mRNA stability. M6A-RIP-qPCR was performed to validate the presence of m6A modifications on EZH2 mRNA. ResultsEZH2 was found upregulated in multiple B-cell subsets from the peripheral blood and SGs of pSS patients, as well as in three different animal models of SS. The expression of EZH2 in B cells was positively correlated with the ESSDAI score, which is a measure of disease activity. With treatment of EZH2 inhibitor, SS-like signs alleviated and autoantibody production reduced in ESS mice. Similarly, in pSS patients, METTL3 expression was increased in the SGs and peripheral blood CD19+ B cells, also showing a positively correlated with the ESSDAI score. With knockdown of METTL3, the expression of EZH2 reduced. Mechanistically, EZH2 inhibited B-cell apoptosis and promoted B-cell proliferation by catalyzing H3K27me3 modification at the CDKN1A locus. Furthermore, METTL3 bound to EZH2 mRNA and increased m6A modification on EZH2 mRNA, enhancing its stability and promoting EZH2 expression. ConclusionsThe upregulation of EZH2 mediated by METTL3 is implicated in the B-cell autoimmune response in pSS. Inhibition of EZH2 presents a promising therapeutic strategy for pSS treatment.

Sjögren's Disease and Gastroesophageal Reflux Disease: What Is Their Evidence-Based Link?

Sjögren's disease (SjD), or primary Sjögren's syndrome (pSS), is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin's lymphoma in mucosa-associated lymphoid tissue. SjD is one of the autoimmune diseases with the maximum delayed diagnosis due to its insidious onset, heterogeneous clinical features and varied course. It is increasingly recognized that extraglandular manifestations represent a clinical challenge for patients with SjD. The European League Against Rheumatism (EULAR) Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary Sjogren's syndrome. It consists of 12 domains: cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and lymphoma, biological. More than a quarter of patients with pSS may have systemic features that are not included in the ESSDAI classification, i.e., various cardiovascular, ophthalmic, ENT, and other systemic or organ involvement that increase the magnitude of the systemic phenotype in the disease. The ESSDAI also excludes the gastrointestinal (GI) tract, and unfortunately, GI manifestations are not routinely assessed. Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders, impairing quality of life and consuming a large volume of medical resources. Recently carried out the Mendelian randomized trial confirmed the causal link between SjD and gastroesophageal reflux disease (GERD) and showed that GERD is a risk factor for SjD. This review aims to provide an overview of the research describing evidenced based links between Sjögren's disease and gastroesophageal reflux disease, with the intention of ensuring that any systemic pathology in Sjögren's disease is properly assessed and that management of the disease is directed towards the patient. A comprehensive literature search was carried out on PubMed, Web of Science, Scopus and the Cochrane Library databases. Two researchers searched for published studies indexed from inception to 1 September 2024 using the keywords 'Sjögren's syndrome' OR 'Sjögren's disease' AND 'gastroesophageal reflux disease' AND 'microbiota' OR microbiota dysbiosis'. We limited our search for scientific articles to human studies, and only included articles in English. Overall, there is a lack of evidence-based studies assessing the association between GERD and Sjögren's disease and the changes in the microbiota associated with GERD in a multidisciplinary setting. Such studies are needed for the future, as this will improve the early diagnosis of Sjögren's disease and the personalized management of the disease.

Lung Disease in Sjögren's Syndrome: Insights From a Reference Center's Population.

Background Sjögren's syndrome (SS) is a chronic systemic autoimmune disorder characterized by lymphocytic infiltration of the exocrine glands. Although primarily affecting these glands, the syndrome can also involve several organs. Interstitial lung disease is one of the most severe complications associated with SS. Objectives This study aims to analyze the characteristics of lung involvement in patients with primary SS from a reference medical center's population. Methods Retrospective, longitudinal study of primary SS patients diagnosed until December 2022. Clinical and laboratory data were collected and subjected to statistical analysis using SPSS®. A 95% confidence interval was considered, with statistical significance set at p<0.05. Results A total of 126 patients were included, 95.2% of whom were females, with a mean age at diagnosis of 50 years. The median EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) at diagnosis was 3, which decreased to 1 at the last evaluation. Based on the ESSDAI lung domain, nine patients presented with lung disease at diagnosis. This number increased to 18 by the last assessment. Thoracic tomography showed lung disease in 30 patients, with bronchiectasis being the most common finding. Ten patients presented with interstitial lung disease. Pulmonary function tests were abnormal in 18 patients, and the diffusing capacity of the lungs for carbon monoxide was reduced in 32. Patients with lung disease were more likely to experience a dry cough (p<0.01), have positive SSA antibodies (p<0.05), antinuclear antibody (ANA) >1/320 (p<0.01), positive rheumatoid factor (p<0.01), and low C4-complement during follow-up (p<0.05). Conclusions The authors found an association between clinical and analytical findings and the presence of lung disease in SS patients. Further research is essential to identify optimal predictors of SS-associated lung disease, facilitating early diagnosis and intervention for both SS and its related lung complications.

Higher Mortality Risk From Ovarian Carcinomas, Small Bowel Neoplasms, and B-Cell and Mucosa-Associated Lymphoid Tissue Lymphomas in Sjögren Syndrome Patients.

To evaluate the impact of the different types of neoplasms and lineages on Sjögren syndrome (SjS) patient mortality. Medical records review study based on the Spanish Hospital Discharge Database and the International Classification of Diseases, Tenth Revision, Clinical Modification coding list. The neoplasm-related deaths in SjS patients with the general population during the period 2016-2019 were compared. A binary logistic regression analysis considering age, sex, tobacco use, and alcohol use was performed to determine the impact of SjS on the risk of dying from each neoplasm group and lineage. In the period studied, 705,557 in-hospital deaths were certified in Spain, 139,531 (19.8%) from neoplasms. Neoplasms surpassed SjS activity as a cause of mortality in primary SjS patients (11.3% vs. 1.6%, p < 0.001). SjS patients presented higher mortality rates from small bowel carcinoma (0.3% vs. 1.8%; odds ratio [OR], 5.41; 95% confidence interval [CI], 1.33-22) and gynecological neoplasms (6.4% vs. 3%; OR, 2.13; 95% CI, 1.01-4.58), related to ovarian carcinomas (4.6% vs. 1.3%; OR, 3.65; 95% CI, 1.48-8.97), than the general population. Hematological neoplasm-related deaths were more prevalent in SjS patients than in the non-SjS population (18.3% vs. 8.9%; OR, 2.04; 95% CI, 1.25-3.31), mostly attributable to the higher proportion of deaths from B-cell non-Hodgkin lymphoma (8.3% vs. 2.5%; OR, 3.04; 95% CI, 1.54-6.03) and mucosa-associated lymphoid tissue lymphoma (1.8% vs. 0.1%; OR, 70.17; 95% CI, 16.61-296.36). SjS patients face an elevated risk of mortality from small bowel neoplasms, ovarian carcinomas, and B-cell and mucosa-associated lymphoid tissue lymphoma compared with the general Spanish population. Apart from developing approaches to mitigate their occurrence, it is crucial to explore thoroughly and consider the implementation of targeted early-detection programs for these specific conditions.

Frexalimab (SAR441344) as a potential multiautoimmune disorder tackling mAB targeting the CD40-CD40L pathway undergoing clinical trials: a review.

Autoimmune disorders exhibit intricate pathology. Their mechanisms are complex, which attenuates the need for novel therapeutic interventions. Frexalimab, a potent monoclonal antibody targeting the dysregulated CD40-CD40L pathway, stands out as a formidable weapon against the assault of inflammation and tissue devastation. Diverse electronic databases were searched using relevant keywords to extract data on the role of Frexalimab in combating various autoimmune diseases. This review highlights Frexalimab's efficacy in improving various disability indicators of relapsing multiple sclerosis (RMS), alleviating fatigue in primary Sjögren's syndrome (PSJS), and improving glycemic control in diabetic patients. Across multiple trials, its favorable safety profile has proven its superiority over first-generation drugs in minimizing side effects. Indeed, Frexalimab has become a harbinger of hope in the fight against autoimmune diseases and has pioneered a unique and unchallenging way for tackling complex autoimmune diseases in the clinical realm, however, further large-scale trials are needed to establish its therapeutic benefits across different autoimmune conditions.

Pulmonary Progressive Fibrosis in Rheumatoid Arthritis and Primary Sjogren Syndrome: Similarities and Differences.

Background: Progressive pulmonary fibrosis (PPF) has been associated with a worse prognosis, even when interstitial lung disease (ILD) is related to rheumatic diseases. Since many differences are detectable among rheumatic diseases in prevalence and features of ILD, we aimed to investigate features of PPF in different rheumatic diseases, namely rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS). Methods: In an Italian multicentre cross-sectional study, consecutive pSS or RA patients with a diagnosis of ILD from at least two years were enrolled. For each patient, demographic, clinical, and serological data, other than chest high-resolution computed tomography and lung function tests, were recorded at the enrolment and after 2 years. Results: Among 232 patients, namely 156 RA-ILD and 76 pSS-ILD, a PPF was recorded in 38.8% of cases, without differences between the two diseases. Analysing patients with a PPF, usual interstitial pneumonia was significantly more frequent in RA than pSS (71.4% and 44.4%, respectively; p = 0.019), while ILD preceded the diagnosis of the rheumatic disease in 29.1% of RA and 89.5% of pSS (p < 0.001). Finally, RA patients were significantly younger than pSS at the diagnosis of the rheumatic disease (p < 0.001). Conclusions: In conclusion, although there is a similar prevalence of PPF in RA-ILD and pSS-ILD, we demonstrated for the first time that the two conditions differ in terms of radiological patterns and demographic and clinical features, suggesting that specific factors related to such diseases might influence the lung involvement over time. Prospective studies could investigate if these specificities could induce different responses to the treatment.

Primary headache in SLE –systematic review and meta-analysis

ObjectivesTo systematically review and synthesize literature on: 1) the overall prevalence of primary headaches and specifically migraines, in patients with lupus since previous systematic review published in 2004; 2) the risk factors associated with primary headaches in patients with lupus; 3) the association of primary headaches with structural brain changes; and 4) “lupus headaches”. MethodsThis review used (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guidelines and literature searches in four databases: Ovid-based Medline, Embase, PsycINFO, and Cochrane Database of Systematic Reviews from inception until 4/2022. Papers on primary headaches in patients with lupus were identified. Included studies were critically appraised and analyzed. Since a systematic review on this topic was published in 2004, only papers published in 2004 and later were included in this review. Statistical and publication bias was assessed using funnel plots. ResultsA total of 5096 references were identified, 189 were selected for detailed review and 11 papers were included in the final analysis. 1) The pooled prevalence of primary headaches in lupus was 26.8 % (95 %CI 25.1–28.6). The prevalence of primary headaches was similar between patients with lupus and healthy controls, odds ratio (OR) 2.14, 95 %CI 0.97–4.76, p value=0.06, however publication bias was significant according to the Egger test. Lupus patients seem to have a higher prevalence of primary headaches compared to patients with rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS), OR 2.5, 95 % CI 1.56–4, p < 0.0001. Regarding the prevalence of migraines specifically, no difference was found between patients with lupus compared to healthy controls and patients with RA or pSS. 2) Primary headaches seem to be associated with depression and impaired health related quality of life rather than lupus activity or damage. There is insufficient data to conclude whether specific lupus treatments affected primary headaches in lupus, however, one study did suggest hydroxychloroquine reduced the frequency of primary headaches. Raynaud phenomenon was associated with migraines. 3) One study which examined MRI scans of patients with lupus compared to healthy controls did suggest that larger gray matter volumes reduced the odds for headaches in general (OR 0.98, p = 0.048) and for migraines in particular (OR 0.95, p = 0.004), and larger white matter volumes increased the odds for migraine (OR 1.04, p = 0.007). However, these findings might reflect disease activity or damage, therefore further studies are required to clarify this issue. 4) The only study which specifically addressed the prevalence of “lupus headaches” is Hanly's study from 2013 of the SLICC cohort. In this large cohort, only 1.5 % of patients had "lupus headaches", as defined by SLE Disease Activity Index-2000 (SLEDAI-2 K). Therefore “Lupus headache” is a rare entity in SLE and should be suspected after excluding other possible explanations for headaches, especially when there is no known prior history of primary headaches. ConclusionsPatients with lupus seem to have a similar prevalence of primary headaches, and specifically migraines, compared to healthy controls. These primary headaches are associated with depression and Raynaud phenomenon and not with disease activity nor damage. Scarce data is published regarding structural changes associated with primary headaches. Currently is seems “lupus headaches” are a distinct rare manifestation of lupus and more data are needed.

Characterization of primary Sjögren's syndrome in the Taiwan Han population through a genome-wide association study and polygenic risk score analysis

BackgroundSjögren's syndrome (SS) is an autoimmune disorder that primarily affects the exocrine glands, leading to dryness of mucous membranes and systemic manifestations. This study aimed to identify genetic markers associated with primary SS (pSS) in the Taiwan Han population through a hospital-based genome-wide association study (GWAS) and polygenic risk score (PRS) analysis, addressing the lack of genetic research. ResultsThis study included 11,390 patients diagnosed with pSS and 113,900 controls. GWAS identified one known locus and eight novel loci. Known HLA alleles, including HLA-DRB1*15:01 and HLA-DQA1*03:01, were successfully replicated in a consistent effect direction. PRS analysis revealed that several autoimmune diseases share similar genetic backgrounds with pSS, including rheumatoid arthritis and systemic lupus erythematosus. ConclusionThis study represents the largest cohort to date on the genetics of pSS in the Taiwan Han population. Our findings provide valuable insights into the pathogenesis of pSS and emphasize the comorbidities associated with it as an autoimmune disease.

An Early View of Iran Primary Sjogren Syndrome Registry (Guilan Province Pilot Phase), an Emerging Effort for a National Registry Establishment

An Early View of Iran Primary Sjogren Syndrome Registry (Guilan Province Pilot Phase), an Emerging Effort for a National Registry Establishment

Rare connective tissue diseases in patients with C1-inhibitor deficiency hereditary angioedema: first evidence on prevalence and distribution from a large Italian cohort study.

In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients. A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age ≥15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria. Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01). A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity.

Characterization of anti-EBNA-1 antibodies and exploration of their molecular mimicry potential in an EBV-infected Sjögren's syndrome patient

There is a potential link between autoimmune diseases and Epstein-Barr virus (EBV) infections, with EBV playing a substantial role in the onset of Sjögren's syndrome (SjS). Some EBV proteins could mimic host self-antigens post-infection, leading to molecular mimicry. This similarity may cause the immune system to attack its tissues mistakenly. Among the various proteins associated with EBV, nuclear antigen 1 (EBNA-1) is essential for the latent replication of infected cells and is prevalent in all EBV-related diseases. In the study, single-chain variable fragment (scFv) antibodies targeting EBNA-1 were isolated using phage display technology from a primary SjS patient who also had a chronic active EBV infection. The specific clones were enriched after panning, and the binding activity of selected scFvs targeting EBNA-1 was confirmed. Sequence analysis indicated that the scFvs exhibiting positive signals could be grouped into five clones, all of which used homologous heavy chain V regions derived from germline Vh4-39, and two types of light chain V regions stemming from germline Vλ1-44 and Vλ3-15. These scFvs were found to exhibit a high degree of somatic mutations, likely indicative of antigen selection. Of the scFvs, P1-3 demonstrated the strongest binding affinity to EBNA-1, exhibiting a determined value of 7.3 x 10−8 M, and showed cross-reactivity to the SjS associated La/SSB self-antigen. The experimental results combined with AlphaFold 3 predictions revealed a potential epitope for scFv P1-3 binding to EBNA-1. Additionally, scFv P1-3 could also cross-bind to the modeled structure of La/SSB. We inferred a possible structural correlation between EBNA-1 and La/SSB involving an X2AX6PG epitope motif. This research contributes to our understanding of the structural basis of the interactions between antibodies and EBNA-1, shedding light on the VH and VL gene usage of anti-EBNA-1 antibodies in EBV-infected SjS patients and the potential origins of autoantibodies.

Epidemiology of Sjogren's syndrome in a sample of the Egyptian population: a cross-sectional study.

To investigate the prevalence of Sjögren's syndrome (SS) and the associated factors in a sample of the Egyptian population. This cross-sectional study obtained data by screening subjects from several hospitals in different governorates across Egypt. Demographic and health data were collected including symptoms and type of Sjögren's syndrome, associated autoimmune diseases, the presence of specific autoantibodies and associated malignancies. The study analysed 7960 participants and 64 (0.80%) had SS. Of these, 22 (34.38%) had primary SS and 42 patients (65.63%) had secondary SS. For the total study cohort, the prevalence of primary and secondary SS was 0.28% and 0.53%, respectively. There was a higher prevalence of SS in females compared with males and SS was more common in the fifth and sixth decades. All patients with SS complained of oral and ocular dryness. The most common concomitant autoimmune disease was rheumatoid arthritis. Anti-SSA (Ro) and anti-SSB (La) antibodies were the most frequently associated autoantibodies. Only two patients had non-Hodgkin's lymphoma. This was the first study to describe the prevalence of SS in Egypt. SS is not a rare disease in Egypt, so raising awareness of SS in both patients and healthcare professionals is very important.