Sjögren's Syndrome Patients Research Articles

Sjögren's syndrome positive for isolated anti-Ro52/SS-A antibody and anti-centromere antibody.

This current case report describes a Japanese woman in her 80s with xerostomia who presented with salivary gland dysfunction. She was positive for isolated anti-Ro52/SS-A antibody as determined by a chemiluminescent enzyme immunoassay and positive on a fluorescence enzyme immunoassay that recognizes both Ro52 and Ro60 antigens. A high serum concentration of anti-Ro52/SS-A antibody was determined by an enzyme-linked immunosorbent assay. A high anti-centromere antibodies (ACA) titre was also observed. Although Raynaud's phenomenon or a high serum immunoglobulin G concentration were not observed, Masson-trichrome staining of the patient's labial salivary glands showed considerable fibrosis. Her serum type I and type II interferon concentrations were normal. The present patient is the first with Sjögren's syndrome (SS) to exhibit isolated anti-Ro52/SS-A antibody and ACA without anti-Ro60/SS-A antibody. This current case report presents her case together with those of four other SS patients who were positive for isolated anti-Ro52/SS-A antibody. The SS literature also includes cases positive for ACA and describes clinical characteristics. The other four SS patients with isolated anti-Ro52/SS-A antibody described here had no ACA; interstitial pneumonia and polyneuropathy were observed in these cases, although there was no consistent tendency regarding types I and II interferon.

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.

Evaluation of traditional Chinese medicine tea bag TBDESJS in patients with Sjögren's syndrome and dry eye syndrome: A phase II pilot study.

Sjögren's syndrome (SJS) and dry eye syndrome (DES) are characterized by ocular dryness from inadequate tear production or excessive evaporation. To evaluate the effectiveness of TBDESJS (Chun-Yu-Ching-Hua-Yin, CYCHY), a TCM tea bag, in treating SJS and DES patients compared with healthy controls (NHC). This phase II pilot study included 100 participants (60 SJS, 30 DES, 10 NHC) across 8 weeks, assessing changes in Schirmer's test, OSDI, ESSPRI, PSQI, FIRST, and artificial tear usage, using repeated measurement ANOVA and Tukey's honestly significant difference (HSD) for analysis. Total 97 subjects completed the trial, for the left eye (OS) of Schirmer's test, significant improvements at 4, and 8 weeks were observed in SJS (0.13 ± 0.43-5.77 ± 2.87, and 7.60 ± 4.84 mm) and DES (0.21 ± 0.41-6.21 ± 2.97, and 7.86 ± 3.47 mm) (all p < .001). For the right eye (OD), significant improvements were observed in SJS (0.13 ± 0.39-6.77 ± 4.53, and 8.79 ± 5.92 mm) and DES (0.34 ± 0.55-6.59 ± 2.50, and 8.24 ± 3.42 mm) (all p < .001). Secondary outcomes showed reduced the dryness of ESSPRI scores in SJS (6.37 ± 1.97-5.57 ± 1.79, p < .001) and DES (6.10 ± 1.97-5.28 ± 2.23, p < .05). PSQI global scores improved significantly in all groups at 8 weeks (p < .05). Artificial tear usage decreased in SJS (4.93 ± 2.45-1.00 ± 0.82 times/day), DES (4.47 ± 1.99-0.66 ± 0.67 times/day) (all p < .001). No serious adverse events in this study. TBDESJS significantly improved tear production, ocular dryness, and sleep quality, indicating potential neural regulation, anti-inflammatory and immunomodulatory benefits. These findings advocate for TBDESJS (Chun-Yu-Ching-Hua-Yin, CYCHY)'s comprehensive therapeutic value in SJS and DES treatment, emphasizing the need for further research to understand long-term effects and mechanisms.

Removable dental prostheses for patients with Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic autoimmune condition primarily affecting the salivary and lacrimal glands, leading to pronounced dry mouth (xerostomia) and dry eyes. These symptoms create unique challenges for SS patients requiring removable dental prostheses, as the lack of saliva significantly impacts the retention, comfort, and overall effectiveness of these devices. Without adequate saliva, prosthetic retention diminishes, and patients frequently experience issues such as mucosal irritation and increased susceptibility to infections. To address these issues, tailored material choices are critical in designing effective prosthetic solutions. Soft liners, moisture-retentive acrylics, and antimicrobial coatings are among the innovations improving both retention and comfort for SS patients. The aesthetic and functional outcomes of prosthetic solutions are also essential considerations. Enhanced retention mechanisms, such as implant-supported overdentures, not only improve masticatory performance but also aid in preserving the patient’s facial profile and lip support. Advanced materials offering translucency and color stability contribute to a more natural appearance, which is critical for patient satisfaction. The maintenance of these prostheses requires specific care routines to mitigate microbial buildup and tissue irritation. Specialized cleaning agents and salivary substitutes help maintain hygiene and reduce discomfort, while regular follow-up visits enable timely adjustments to accommodate tissue changes and extend the prosthesis lifespan. Implementing a comprehensive approach that considers material selection, functional and aesthetic outcomes, and maintenance strategies can greatly enhance the quality of life for SS patients. By understanding and addressing the specific needs associated with xerostomic conditions, dental professionals can provide prosthetic solutions that offer both reliability and comfort in this challenging context. Regular patient education and diligent care routines remain essential to ensure the long-term success and durability of removable dental prostheses for individuals with SS.

Increased expression of CXCL10 and CCL3 salivary gland chemokines in primary Sjögren's syndrome detected and systematically quantified using novel RNAscope® in situ hybridisation.

Primary Sjogren's syndrome is a chronic inflammatory disease characterised by the destruction of exocrine glands. We have previously shown significantly upregulated levels of CXCL10 and CCL3 chemokines in saliva from Sjogren's syndrome patients. In this study, we examined the expression pattern and localisation of these chemokines at the site of inflammation in patients' minor salivary glands using novel RNAscope® in situ hybridisation. Minor salivary glands from 33 primary Sjogren's syndrome patients and 22 non-Sjogren's syndrome sicca controls were included. The biopsies were formalin- fixed, paraffin-embedded and histopathologically evaluated. The CXCL10 and CCL3 mRNA expression in the glandular tissue was investigated using reverse transcription quantitative real-time polymerase chain reaction followed by RNAscope® in situ hybridisation. The mRNA expression of CXCL10 was higher than CCL3 in all patients. Significantly elevated expression of CXCL10 and CCL3 was detected in patients that also expressed autoantibody positivity and a positive biopsy for mononuclear cell infiltrates when compared to controls. CXCL10 was localised as clusters within focal infiltrates as well as adjacent to acinar and ductal epithelium, while CCL3 was expressed as scattered single mRNA molecules in focal infiltrates and in acinar cells. Our findings suggest CXCL10 as a possible disease biomarker in primary Sjogren's syndrome due to its upregulated expression in both saliva and minor salivary glands of patients and the localisation in the tissue. This should be re-assessed in a larger primary Sjogren's syndrome patient cohort, followed by additional functional studies to further validate its potential as a disease biomarker.

Associations between Sjogren syndrome and psychiatric disorders in European populations: a 2-sample bidirectional Mendelian randomization study.

Psychiatric disorders, such as major depressive disorder (MDD), anxiety disorder (AD), bipolar disorder (BD), and schizophrenia (SCZ), are disturbances in brain activity that lead to disorders of cognition, behavior, and emotion regulation. Among Sjogren syndrome (SS) patients, psychiatric disorders are more prevalent than in the general population. Identifying associated risk factors can provide new evidence for clinical diagnosis and treatment. We selected genetic instruments based on published genome-wide association studies (GWASs) to determine predisposition. Then, we conducted a 2-sample bidirectional Mendelian randomization (MR) analysis to explore the potential causal associations between SS and four major psychiatric disorders. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using MR-Egger, MR-PRESSO, and "leave-one-out" method methods. Our study showed that SS was linked to BD and SCZ, indicating that individuals with SS may have a reduced risk of developing BD (IVW: OR = 0.940, P=0.014) and SCZ (IVW: OR = 0.854, P=1.47*10-4), while there was no causal relationship between SS and MDD or AD. MR-Egger regression shows no evidence of pleiotropy (BD: intercept = 0.007, p = 0.774; SCZ: intercept = 0.051, p = 0.209). The same as the MR-PRESSO analysis (BD: global test p = 1.000; SCZ: global test p = 0.160). However, the results from the leave-one-out analysis demonstrated instability. Specifically, after excluding SNP rs3117581, the effects on BD and SCZ were found to be non-significant, suggesting the potential influence of unrecognized confounding factors. The results of the reverse MR show that four major psychiatric disorders had no causal effects on SS. Our research findings demonstrate a causal relationship between SS and SCZ, as well as between SS and BD. There are no causal effects between the four major psychiatric disorders and SS. These findings suggest that SS may have the potential to reduce the risk of both psychiatric disorders. This study provides new insight for their prevention and treatment.

Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren’s syndrome

Some forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging.

Subpopulation dynamics of T and B lymphocytes in Sjögren's syndrome: implications for disease activity and treatment.

Sjögren's syndrome (SS) is an autoimmune disorder primarily affecting the body's exocrine glands, particularly the salivary and lacrimal glands, which lead to severe symptoms of dry eyes and mouth. The pathogenesis of SS involves the production of autoantibodies by activated immune cells, and secretion of multiple cytokines, which collectively lead to tissue damage and functional impairment. In SS, the Immune interaction among T and B cells is particularly significant. Lymphocytic infiltration in the salivary glands is predominantly composed of CD4+ T cells, whose activation cause the death of glandular epithelial cells and subsequent tissue destruction. The excessive activity of T cells contributes significantly to the disease mechanism, with helper T cells (CD4+) differentiating into various subgroups including Th1/Th2, Th17, as well as Treg, each contributing to the pathological process through distinct cytokine secretion. In patients with SS, B cells are excessively activated, leading to substantial production of autoantibodies. These antibodies can attack self-tissues, especially the lacrimal and salivary glands, causing inflammation and tissue damage. Changes in B cell subpopulations in SS patients, such as increases in plasmablasts and plasma cells, correlate positively with serum autoantibody levels and disease progression. Therapies targeting T cells and B cells are extensively researched with the aim of alleviating symptoms and improving the quality of life for patients. Understanding how these cells promote disease development through various mechanisms, and further identifying novel T and B cell subgroups with functional characterization, will facilitate the development of more effective strategies to treat SS.

Analysis of risk factors and development of a nomogram prediction model for renal tubular acidosis in primary Sjogren syndrome patients

ObjectiveTo 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.MethodData 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.ResultsA 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.DiscussionWe 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.

The evaluation of the short-term and long-term hydroxychloroquine therapy on ECG parameters.

Amidst the COVID-19 pandemic, hydroxychloroquine (HCQ) was widely administered despite limited data on its safety and efficacy. This study assesses the acute and chronic impacts of HCQ on electrocardiography (ECG) parameters alongside the effects of azithromycin and levofloxacin coadministration in patients with COVID-19. A comprehensive analysis was conducted on 109 COVID-19 patients receiving HCQ, with or without Azithromycin and/or Levofloxacin, and 51 long-term HCQ-treated Sjogren's syndrome (SS) patients. ECG parameters, including QTc interval, were meticulously evaluated against a control group of 109 COVID-19 patients without HCQ treatment. HCQ monotherapy, in combination with Levofloxacin, significantly prolonged the QTc interval in COVID-19 patients compared to controls. Notably, the combination of HCQ and Azithromycin demonstrated a mitigated impact on QTc prolongation. Long-term HCQ use in SS patients did not significantly affect QTc intervals, illustrating a distinct safety profile from short-term use in COVID-19 treatment. HCQ's impact on QTc prolongation is influenced by therapeutic context, coadministered drugs, and patient demographics. The findings underscore the necessity of cautious HCQ use, particularly in acute settings like COVID-19, where monitoring and consideration of drug interactions and patient-specific factors are critical.

Subjective Symptoms and Disease Activity Related to Serum Zinc Concentration in Primary Sjögren's Syndrome.

Background/Objectives: We examined the frequency of zinc deficiency in patients with Sjögren's syndrome (SS) and the relationship between zinc deficiency and each of the subjective symptoms and disease activity. Methods: We enrolled 164 patients aged ≥ 20 years with primary SS (pSS) based on the revised diagnostic criteria of the Ministry of Health, Labor and Welfare (1999) and 144 patients with RA diagnosed according to the ACR/EULAR classification criteria for RA (2010) as a comparison group. Subjective symptoms were confirmed using an original questionnaire, and disease activity was determined using the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI). The serum zinc concentrations were measured in both SS and RA patients. Results: The rate of zinc deficiency in the SS group was 26.1%, significantly higher than that in the RA group (7.6%). The rate of zinc deficiency was significantly higher in the pSS group compared with Japanese health checkup recipients reported in the literature. The mean serum zinc concentration in primary SS was 60.6 ± 7.3 µmol/L in the high disease activity group with an ESSDAI of ≥5 points, which was significantly lower than the concentration of 69.7 ± 10.2 µmol/L in patients with an ESSDAI of ≤4 points. Conclusions: The frequency of zinc deficiency was higher in patients with pSS than in patients with RA. Disease activity was also higher in patients with zinc deficiency, suggesting an association between zinc concentration and organ involvement in pSS.

Case Series of Changes in Greyscale and Power Doppler Signals on Salivary Gland Ultrasonography after Treatment in Patients with Sjögren's Syndrome.

The usefulness of greyscale (GS) in salivary gland ultrasonography for Sjögren's syndrome (SS) has been established; however, limited information is currently available on power Doppler signals (PDs), and changes after treatment remain unknown. PDs are considered to represent glandular inflammation, which indicates the worsening of GS in later years. We examined the changes in PDs in three immunosuppressant-treated SS patients. PDs decreased, along with GS and markers of disease activity, after treatment. PDs have the potential to provide insights into glandular inflammation in real time; however, large-scale studies on their clinical usefulness are needed.

Role of mucosal-associated invariant T cells dynamics in pathogenesis of Sjögren syndrome

Sjögren syndrome (SS) is an autoimmune disease characterized by chronic inflammatory infiltrates in the salivary and lacrimal glands. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T-cells, predominantly found in mucosal tissues with crucial role in epithelial homeostasis. Thus, MAIT cells may be implicated in mucosal alterations of SS patients. Activation markers, inflammatory and cytotoxic cytokines were examined in 23 SS patients and compared to 23 healthy controls (HC). Tissular MAIT cells in salivary gland (SG) biopsies were also analyzed. Circulating MAIT cells were decreased in SS patients with a higher expression of CD69 and a higher CD4/CD8 ratio of MAIT cells. MAIT cells showed a higher production of IFNγ, TNFα and GzB in SS compare to HC. Tissular MAIT cells were present within inflamed SG of SS patients, while they were absent in SG of HC. Overall, circulating MAIT cells are decreased in the peripheral blood of SS albeit producing higher amounts of IFNγ, TNFα, and GzB. Tissular MAIT cells are detected in salivary glands from SS with a proinflammatory tissular cytokine environment. MAIT cells with abnormal phenotype, functions and tissular homeostasis may contribute to epithelial damage in SS.

G protein-coupled receptor kinase 2 as a novel therapeutic target for gland fibrosis of Sjögren's syndrome.

Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by gland fibrosis. We previously found a close correlation between gland fibrosis and the expression of G protein-coupled receptor kinase 2 (GRK2). In this study we explored the pathological and therapeutic significance of GRK2 in SS. Submandibular gland (SMG) antigen-induced SS mouse model was established in WT and GRK2+/- mice. We showed that the expression levels of GRK2 were significantly up-regulated in glandular tissue and positively correlated with fibrotic morphology in SS patients and mice. Hemizygous knockout of GRK2 significantly inhibited the gland fibrosis. In mouse salivary gland epithelial cells (SGECs), we demonstrated that GRK2 interacted with Smad2/3 to positively regulate the activation of TGF-β-Smad signaling with a TGF-β-GRK2 positive feedback loop contributing to gland fibrosis. Hemizygous knockout of GRK2 attenuated TGF-β-induced collagen I production in SGECs in vitro and hindered gland fibrosis in murine SS though preventing Smad2/3 nuclear translocation. Around 28 days post immunization with SMG antigen, WT SS mice were treated with a specific GRK2 inhibitor paroxetine (Par, 5 mg·kg-1·d-1, i.g. for 19 days). We found that Par administration significantly attenuated gland fibrosis and alleviated the progression of SS in mice. We conclude that genetic knockdown or pharmacological inhibition of GRK2 significantly attenuates gland fibrosis and alleviates the progression of SS. GRK2 binds to Smad2/3 and positively regulates the activation of TGF-β-Smad signaling. A TGF-β-GRK2 positive feedback loop contributes to gland fibrosis. Our research points out that GRK2 could be a promising therapeutic target for treating SS.

Clinical features and risk factors for Sjogren’s syndrome patients suffering from oral candidiasis in Shanxi, China

ObjectivesTo investigate the clinical features and risk factors of Sjogren’s Syndrome (SS) patients suffering from oral candidiasis and to provide a foundation for the prevention and treatment of oral candidiasis in SS patients.MethodsThe medical records of 479 SS patients admitted to the Second Hospital of Shanxi Medical University from 2018 to 2020 were analysed to determine the clinical characteristics and risk factors that influence the occurrence of oral candidiasis infection in SS patients.ResultsPatients with oral candidiasis were older than those without oral candidiasis (P < 0.05). Male SS patients had greater oral candidiasis rates (P < 0.05). Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were both shown to be adversely associated with oral Candida infections (P < 0.001). Logistic regression revealed that a low UWS was an independent risk factor for oral Candida infections in SS patients (OR: 0.004, P = 0.023). Greater WBC counts (OR: 1.22, P < 0.001), lower haemoglobin levels (OR: 0.97, P = 0.007), lower serum albumin levels (OR: 0.88, P < 0.001), lower IgG levels (OR: 0.91, P = 0.011), lower IgA levels (OR: 0.75, P = 0.011), and lower IgM levels (OR: 0.91, P = 0.015) were found in patients with oral Candida infections. Patients on immunosuppressive medications (OR: 0.32, P = 0.011), particularly rapamycin (P < 0.001), had a decreased rate of oral Candida infections.ConclusionsPatients with oral candidiasis were older than those without oral candidiasis. Male SS patients are more likely to have oral candidiasis. Individuals with lower UWS and SWS are more susceptible to oral Candida infection. Oral Candida infections in SS patients depend on their immunological status. Rapamycin may increase the abundance of Treg cells to reduce oral Candida infection in SS patients.

Polyarthritis in Sjögren's Syndrome: Difficulties in Distinguishing Extraglandular Manifestation and Associated Rheumatoid Arthritis.

Aim of the study was to investigate the demographic data and disease course characteristics of patients with Sjögren's syndrome (SS) and inflammatory joint pain of various origins and to search for factors that might help with the distinction of polyarthritis as an extraglandular manifestation and rheumatoid arthritis as an associated systemic autoimmune disorder. A total of 355 patients were retrospectively analyzed, 128 of whom served as controls (SS-C), while 159 had polyarthritis as an extraglandular symptom of Sjögren's syndrome (SS-pa) and 68 were diagnosed as having associated rheumatoid arthritis (SS-RA). The patients without any inflammatory joint manifestations were significantly older than the SS-pa patients, while, for the SS-RA group, the difference was not significant. The onset of joint pain appeared significantly earlier in the SS-RA patients. Regarding either extraglandular manifestations or associated autoimmune disorders, there were significant differences between the controls and both SS-pa and SS-RA groups, while no significant difference was found between the SS-pa and SS-RA groups. Thus, laboratory and imaging methods should be used to differentiate between the two conditions, but laboratory biomarkers are even more important for early diagnosis. A ROC curve analysis showed an acceptable diagnostic accuracy in differentiating between SS-pa and SS-RA patients using a binary logistic regression model, where highly positive rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) values, kidney involvement, and anti-Ro/SS-A positivity were shown to significantly raise the odds of having RA, whereas anti-La/SS-B positivity seemed to have a protective role, since it significantly decreased the odds of having it. Further biomarkers are needed to better classify SS patient cohorts with inflammatory joint pain of different origins and, consequently, different management requirements.

Relationship between Sjogren's syndrome and gastroesophageal reflux: A bidirectional Mendelian randomization study

The clinical incidence of sjogren's syndrome combined with gastroesophageal reflux disease is high. Existing observational studies have shown inconsistent results in the association between gastroesophageal reflux disease (GERD) and Sjogren's syndrome (SS).We observed that the symptoms of SS patients also improved after receiving GERD-related treatment. Therefore, we aimed to investigate the relationship between GERD and SS through a bidirectional two-sample Mendelian randomization (MR) study. Independent SNPs associated with GERD and SS were selected from a genome-wide association study (GWAS) as instrumental variables to conduct a bidirectional two-sample Mendelian analysis of GERD and SS. Genetic data were obtained from two databases for the following two outcomes: Gastroesophageal reflux (IEU Open GWAS) [sample size = 602,604 (patients = 129,080; nonpatients = 473,524)] and SS (FinnGen) [sample size = 392,423 (patients = 2,495; nonpatients = 389,928)]. Statistical methods for the MR analysis included the inverse-variance weighting method, weighted median, simple mode and weighted mode, as well as heterogeneity and sensitivity analyses using the Cochran Q statistic, MR‒Egger regression, outlier detection methods (MR-PRESSO). In addition, Steiger Test was conducted to test the direction of causality. MR analysis showed a positive correlation between GERD and SS risk [odds ratio (OR) = 1.3279 (95% confidence interval 1.0312–1.7099, P = 0.0280)]. However, in contrast, no significant causal effect of SS on GERD was observed [OR = 1.0024 (95% CI 0.9651–1.0412; P = 0.8995)]. This bidirectional two-sample Mendelian randomization study confirmed a causal relationship between SS and GERD, and suggested that GERD is a risk factor for SS, while SS does not affect GERD.

Particularités du Syndrome de Sjögren chez le sujet âgé

Diagnosis of Sjögren syndrome (SS) can be difficult in the elderly in whom sicca syndrome can be related to senescence, comorbidities or to iatrogenesis. We performed a retrospective study including of SS patients records (AECG criteria) in the internal medicine departement, La Rabta Hospital over 18 years. Epidemiological, clinical, biological and therapeutic features of elderly patients (EP) and young patients(YP) were compared Results: A total of 323 patients with SS were enrolled, 35 were over 65 years of age (33 females/2 males). The mean age at disease onset was 68.8±4.4 years. Comparative analysis showed that SS diagnosis was made earlier in elderly (p=0.02). Fatigue was more frequent in elderly (p<0.01). Positivity of anti-SSA was more frequent in YP (p=0.04). Anti-malarial agents were less prescribed in elderly (p=0.03). There was no significant differences concerning the other clinical features, laboratory findings, treatment and outcomes. The SS in elderly seems not to be a distinct subset of disease. However, treatment and follow-up of elderly patients with SS must obey to closer attention considering their vulnerability and the complexity of their management.

Beta-adrenergic stimulation promotes an endoplasmic reticulum stress-dependent inflammatory program in salivary gland epithelial cells.

The effect of beta-adrenergic stimulation on human labial minor salivary gland epithelial cells (LMSGEC) on IL-6 production and its dependency on endoplasmic reticulum (ER) stress were investigated. Primary LMSGEC from Sjögren's syndrome (SS) patients and controls in culture were stimulated with epinephrine and IL-6 expression was evaluated by qPCR and ELISA. The expression of β-ARs in cultured LMSGEC was tested by qPCR, while adrenoceptors and cAMP levels were examined in LMSGs by immunofluorescence. ER evaluation was performed by transmission electron microscopy (TEM) and ER stress by western blot. Epinephrine-induced IL-6 production by cultured LMSGEC was evaluated after alleviation of the ER stress by applying tauroursodeoxycholic acid (TUDCA) and silencing of PKR-like ER kinase (PERK) and activating transcription factor 4 (ATF4) RNAs. Expression of IL-6 by LMSGEC was upregulated after β-adrenergic stimulation, while the silencing of adrenoreceptors downregulated IL-6. The amelioration of ER stress, as well as the silencing of PERK/ATF4, prevented epinephrine-induced upregulation of IL-6. Adrenergic stimulation led to higher and sustained IL-6 levels secreted by LMSGEC of SS patients compared to controls. Adrenergic signaling was endogenously enhanced in LMSGEC of SS patients (expression of β-ARs in situ, intracellular cAMP in cultured LMSGEC). In parallel, SS-LMSGEC expressed dilated ER (TEM) and higher levels of GRP78/BiP. PERK/ATF4 pathway of the ER stress emerged as a considerable mediator of adrenergic stimulation for IL-6 production by the LMSGEC. An enhanced endogenous adrenergic activation and a stressed ER observed in SS-LMSGEC may contribute to a sustained IL-6 production by these cells after adrenergic stimulation.

Co-Existence of Dry Mouth, Xerostomia, and Focal Lymphocytic Sialadenitis in Patients with Sjögren’s Syndrome

Background: Some patients with Sjögren’s syndrome (SS) do not develop xerostomia despite advanced involvement of the salivary glands and the presence of focal lymphocytic sialadenitis (FLS). The aim of the study is to determine possible correlations between xerostomia, symptoms of sicca syndrome, FLS, and other features in SS patients. Methods: The study group comprised 50 patients with SS. The comprehensive assessment of patients included clinical, laboratory, and serological examinations. All patients underwent labial salivary gland biopsies. Dry mouth and dry eyes were assessed by unstimulated whole salivary flow rate (USWSF) and Schirmer’s test, respectively. Results: Xerostomia and xerophthalmia are closely related components of sicca syndrome. Xerostomia did not correlate with any serological or laboratory values, including ANA titers, SSA, SSB, Ro52 antibodies, rheumatoid factor, C-reactive protein, and Erythrocyte Sedimentation Rate. There were no correlations between xerostomia and FLS or Focus score. USWSF results correlated with xerostomia reported by patients, contrary to Schirmer’s test, which did not correlate with xerophthalmia. Conclusions: Dry mouth in SS is independent of any serological or inflammatory parameters. The occurrence of FLS does not determine xerostomia and its severity. Dry mouth in SS is influenced by other undetermined factors and mechanisms independent of salivary gland involvement.