Sjögren's Syndrome Research Articles

Sjogren's Syndrome Complicated by Naso-Orbito-Cerebral Mucormycosis: A Case Report.

Background: Sjogren's syndrome (SS) is a chronic inflammatory autoimmune disease characterized by exocrine gland dysfunction. Mucormycosis is a rare yet life-threatening opportunistic fungal infection caused by Mucor species, with a high mortality rate. In patients undergoing long-term immunosuppressive therapy or corticosteroid use, especially when compounded by conditions such as diabetes or hyperlipidemia, Mucor can become pathogenic. Medical Record Description: We retrospectively analyzed the clinical data of a patient with Sjogren's syndrome complicated by rhinocerebral mucormycosis, focusing on its clinical presentation and progression. The patient was admitted to the hospital 20 days prior with symptoms of a "nasal infection" caused by a furuncle on the nose. The condition progressively worsened, resulting in nasofacial skin ulceration and necrosis, with black eschar formation around the affected area. Upon admission, comprehensive evaluations, including rapid histopathological and fungal tests, confirmed the diagnosis of mucormycosis. Despite surgical intervention under general anesthesia and antifungal therapy, the clinical outcome was ultimately fatal. Conclusion: Mucor infections commonly occur in patients with immunodeficiency and severe underlying diseases. The clinical manifestations are diverse, often presenting with skin tissue necrosis and the formation of black eschar. Fungal culture and histopathological examination remain the gold standards for diagnosing mucormycosis, while imaging studies are crucial for evaluating the extent of fungal dissemination and bone involvement. Given the rapid progression of the disease, early diagnosis and prompt treatment are critical for improving survival rates.

Oral health-related quality of life in primary Sjögren's Syndrome.

Primary Sjögren Syndrome (pSS) is an autoimmune disease that usually affects salivary glands. Research about the impact of oral health in quality of life of patients with pSS is scarce. to describe the characteristics of oral involvement in patients with pSS; To assess quality of life related to oral health (QOL-OH); to determine association between QOL-OH and saliva production, disease activity, and damage. An observational, analytical and cross-sectional study was conducted. Patients aged ≥18 years with pSS were included. Primary outcome was assessed by the Oral Health Impact Profile (OHIP14sp). The EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI), the EULAR Sjögren's syndrome Disease Activity Index (ESSDAI), the Sjogren's Syndrome Damage Index (SSDI) and a Visual Analogue Scale (VAS) for xerostomia, were performed. A dentist evaluated the Decayed, Missing, and Filled Permanent Teeth index (DMFT), O'Leary index (OLI) and Loe & Silnes index (LSI). A multiple linear regression model was performed, taking OHIP14sp as the dependent variable. 51 patients were included. Mean age 54 (±13 years). The OHIP-14sp median was 16 [6-25], xerostomia VAS median was 60 [30-80]. Mean of ESSPRI: 4 (± 2.6), ESSDAI median: 0 [0-2], SSDDI median: 3 [2-4]. Oral involvement occurred in 100% of patients, DMFT median: 22 [14-28], OLI median: 21[13-30]. In the univariate analysis, OHIP14sp was significantly associated with ESSPRI (β2 95%CI 0.72-3.3), xerostomia VAS (β0.19 95%CI 0.08-0.29) and category 2 of the LSI (β: 18 95% CI: 5-31). In the multivariate analysis, OHIP14sp was independently and significantly associated with xerostomia VAS (β0.19 95%CI 0.09-0.29) and category 2 of LSI (β19 95% CI: 7.7-29.7). These findings demonstrate the effects of xerostomia on daily life of patients influencing not only their oral health but also their quality of life.

Neuropsychiatric manifestations in systemic lupus erythematosus and Sjogren's disease.

Autoimmune diseases often present in a systemic manner, affecting various organs and tissues. Involvement of the central and peripheral nervous system is not uncommon in these conditions and is associated with high morbidity and mortality. Therefore, early recognition of the neuropsychiatric manifestations associated with rheumatologic diseases is essential for the introduction of appropriate therapies with the objective of providing a better quality of life for individuals. To provide a literature review of the neuropsychiatric manifestations related to Systemic Lupus Erythematosus (SLE) and primary Sjögren's Disease (pSD), through the description of signs, symptoms, and immunological variables associated with these conditions. A literature review was conducted by searching for national and international articles available in the SciELO and PubMed databases related to the description of neurological and psychiatric manifestations in patients with the rheumatologic diseases of interest in this study. The main NP manifestations presented in SLE and pSD are discussed, focusing on clinical presentation and etiology. Treatment option are, however, mainly based on expert opinion, since a few randomized controlled trials have been done. There is a high prevalence of neuropsychiatric manifestations associated with SLE and pSD. The variety of physiopathology pathways may explain the variety of symptoms, however pathological findings are rare. Multicenter studies on attribution protocols and treatment are necessary to address the current gaps.

Systemic disease activity measured with ESSDAI varies largely over 5 years in a prospective, longitudinal cohort of patients with Sjögren’s disease

ObjectivesThe objectives are to evaluate variation in systemic disease activity (European Alliance of Associations For Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI)) over time at group and individual patient...

Psoriasis increases the risk of Sjögren’s syndrome: evidence from a propensity score-matched cohort study and transcriptomic analysis

BackgroundDespite the well-documented immune dysregulation in both psoriasis and Sjögren’s syndrome (SS), the specific link between these two autoimmune diseases has not been extensively explored. The present study aims to investigate the impact of psoriasis on the risk of SS.MethodsA retrospective cohort study using TriNetX data compared SS development in patients with psoriasis and controls using propensity score matching, Kaplan–Meier curves, and Cox models. Transcriptome data were analyzed to identify shared differentially expressed genes and pathways between the two diseases.ResultsA total of 293,905 patients with psoriasis and an equal number of individuals without psoriasis were included. After propensity score matching, the baseline characteristics of both groups were balanced. During the follow-up period, 3339 patients with psoriasis and 1937 individuals without psoriasis developed SS. The Kaplan–Meier curves indicated a significantly higher risk of developing SS in the psoriasis group compared to the non-psoriasis group. Upon adjustment for multiple confounding factors, the risk of developing SS in the psoriasis group was 50% higher in the psoriasis group than the non-psoriasis group (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.42–1.58). Subgroup analyses confirmed the elevated risk of SS associated with psoriasis. Patients with psoriatic arthritis (PsA) and those treated with biological agents had an even higher risk of developing SS. Transcriptomic analysis revealed potential shared pathogenesis of psoriasis and SS involving cellular proliferation, immune cell recruitment, cytokine secretion, and the interferon response to viral infections.ConclusionsPsoriasis might increase the risk of developing SS, which is augmented by PsA. The overlapping immunological mechanisms may underlie the co-occurrence of psoriasis and SS.

Impact of Sjögren’s disease on quality of sexual life using the Qualisex score

ObjectiveThis study aimed to assess the impact of Sjögren disease (SjD) on the quality of sexual life and its determinants using the Qualisex questionnaire.MethodsThe Qualisex questionnaire was administered to participants...

The Role of the Toll-Like Receptor Signaling Pathway in Autoimmune Diseases and Treatment with Traditional Chinese Medicine: A Literature Review.

Toll-Like Receptors (TLRs) is a pattern recognition receptor that connects innate and adaptive immunity and participates in inflammatory responses play a key role in common autoimmune diseases such as Rheumatoid Arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, and Sjögren's syndrome (SS) by participating in antigen recognition, immune cell activation, and inflammatory factor release. Due to the multi-component and multi-target characteristics of traditional Chinese medicine (TCM), the role of TCM active ingredients acting on TLRs has been widely studied. This article describes the relationship between TLR and four autoimmune diseases, as well as a review of the efficacy of TLR intervention by active ingredients of traditional Chinese medicine. To provide some basis for the future clarification of the mechanism of action of drugs for autoimmune diseases and to assist in the development of new medicines.

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.

Fecal metabolomic analysis of the role of gut microbiota and short-chain fatty acids in the therapeutic mechanism of Timosaponin AIII in Sjögren's syndrome.

Sjogren's syndrome (SS) is a chronic inflammatory and difficult-to-treat autoimmune disease. Timosaponin AIII (TAIII), a plant-derived steroidal saponin, effectively inhibits cell proliferation, induces apoptosis, and exhibits anti-inflammatory properties. This study explored the mechanisms of action of TAIII in SS treatment by studying gut microbiota and short-chain fatty acids (SCFAs) using fecal metabolomics. The model group used non-obese diabetic (NOD) mice. The treatment group was classified into TAIII and hydroxychloroquine groups. The gut microbiota, SCFAs, and metabolites were analyzed using 16S rRNA sequencing, gas chromatography-mass spectrometry analysis, and liquid chromatography-mass spectrometry, respectively. TAIII effectively alleviated dry mouth in NOD mice, slowed the progression of salivary gland tissue injury, reduced inflammatory factor expression, and increased the levels of aquaporins 1 and 5. TAIII regulated SCFA content and tryptophan metabolism by altering the abundance of the Rikenellaceae_RC9_gut_group, thereby reducing the inflammatory response. TAIII can improve imbalances in the gut microbiota and the metabolic levels of related SCFAs and tryptophan, thereby reducing the level of inflammation. The significant differences observed in the abundance of the Rikenellaceae_RC9_gut_group between the treatment and control groups indicated the potential relationship between bacteria and metabolites in SS. Key Points • The safe and effective treatment of SS with traditional Chinese medicine • Multi-means study on intestinal flora, short-chain fatty acids, and metabonomics.

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.

Potassium-Rich, Gluten-Free Diets for Patients with Sjögren's Syndrome: A Hypothesis.

Sjögren's syndrome (SS) is an autoimmune disease and its management is palliative. There is no specific dietary protocol for SS patients. A gluten-free diet has been tested in SS patients with celiac disease (CD) and indicated modest improvements. Whether gluten-free diets per sè could alleviate autoimmune inflammatory processes in the salivary glands of SS patients with associated CD or even in SS patients without CD is an interesting hypothesis and warrants clinical studies. Hypokalemia in SS patients is among the most frequent sequelae of renal tubular acidosis. Supplementation with potassium (K)-rich diets can reduce inflammation and oxidative stress. K level in CD patients is highly abnormal at diagnosis and gluten-free diets help to normalize its serum level in CD patients. Furthermore, treatment of severe cases of SS requires concomitant glucocorticoid therapy and K supplementation. Results of two separate clinical trials in (i) patients with rheumatoid arthritis (RA) -a disease with similar pathology to SS- indicated that the enhanced serum cortisol followed K supplementation, and in (ii) celiac patients, serum K levels were normalized after the administration of a gluten-free diet. We reviewed the literature extensively on this topic to propose a hypothesis to address this problem and suggest a novel potential for K-rich, gluten-free diets in SS patients. Based on causal associations, we propose that higher K absorption and cortisol secretion following gluten-free diets accompanied by K-rich diets in SS patients with low serum potassium levels, may confer a higher therapeutic potential. Clinical trials are needed to test this hypothesis.

A Review of the Impact of Sjögren's Syndrome and/or the Presence of Anti-Ro/SS-A Antibodies on Therapeutic Strategies for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an immune-mediated disease characterized by polyarthritis that affects the small joints of the bilateral upper and lower extremities. RA shares several common clinical symptoms with Sjögren's syndrome (SS), another rheumatic disease caused by the lymphocytic infiltration of exocrine glands, with dry eye and dry mouth being the two most common symptoms. Anti-Ro/SS-A antibodies, a diagnostic biomarker of SS, are positive in patients with RA at a certain rate. The coexistence of SS and/or positivity for anti-Ro/SS-A antibodies in patients with RA influences disease activity and the effectiveness of several classes of disease-modifying antirheumatic drugs (DMARDs). Furthermore, RA, SS, and certain DMARDs, including methotrexate, are associated with the onset of lymphoproliferative disorders (LPD). In contrast, several biological DMARDs, such as tocilizumab and rituximab, are plausible options without the risk of LPD relapse. Considering the results of the studies introduced in this article, RA with SS and/or positivity for anti-Ro/SS-A antibodies could be considered a phenotype different from isolated RA from the perspective of refractoriness to DMARD therapy and LPD risk. Hence, rheumatologists should observe caution when choosing DMARDs. Further studies are needed to establish the appropriate treatment for patients with RA, SS, and/or the presence of anti-Ro/SS-A antibodies.

Exosomes in Autoimmune Diseases: A Review of Mechanisms and Diagnostic Applications.

Exosomes, small extracellular vesicles secreted by various cell types, have emerged as key players in the pathophysiology of autoimmune diseases. These vesicles serve as mediators of intercellular communication, facilitating the transfer of bioactive molecules such as proteins, lipids, and nucleotide. In autoimmune diseases, exosomes have been implicated in modulating immune responses, oxidative stress, autophagy, gut microbes, and the cell cycle, contributing to disease initiation, progression, and immune dysregulation. Recent advancements in exosome isolation techniques and their molecular characterization have paved the way for exploring their clinical potential as biomarkers and therapeutic targets. This review focuses on the mechanisms by which exosomes influence autoimmune disease development and their potential clinical applications, particularly in diagnosis. The role of exosomes in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), inflammatory bowel disease (IBD), and Sjögren's syndrome (SS), is discussed in relation to their involvements in antigen presentation, T-cell activation, and the induction of inflammatory pathways. Additionally, exosome-based biomarkers offer promising non-invasive diagnostic tools for early diagnostic, disease monitoring, and therapeutic response assessment. However, challenges such as standardization of exosome isolation protocols and validation of their clinical significance remain. This review highlights the potential of exosomes as both diagnostic biomarkers and therapeutic targets in autoimmune diseases, emphasizing the need for further research to overcome current limitations and fully harness their clinical value.

A human oral commensal-mediated protection against Sjögren’s syndrome with maintenance of T cell immune homeostasis and improved oral microbiota

Sjögren’s syndrome (SS) is a prevalent systemic autoimmune disease with substantial impacts on women’s health worldwide. Although oral Haemophilus parainfluenzae is reduced in SS, its significance remains unclear. This study aimed to elucidate the pathophysiological role of H. parainfluenzae in SS. Reduced salivary H. parainfluenzae levels in SS patients were confirmed through quantitative PCR. Oral H. parainfluenzae inoculation in NOD mice alleviated focal sialadenitis, improved salivary function, and reduced IFN-γ+CD3+ and IFN-γ+CD8+ T cells in salivary gland-draining lymph nodes, maintaining immune homeostasis against a biased type 1 response. Inoculation also enhanced salivary microbiota diversity, balanced the Firmicutes-to-Proteobacteria ratio, and reduced the overwhelming presence of Pseudomonas mendocina. In vitro, H. parainfluenzae-preconditioned A253 cells limited CD8 T cell expansion with reduced IFN-γ production. These findings suggest that H. parainfluenzae improves oral microbial diversity, promotes homeostatic T-cell immunity, and protects against SS, supporting its potential as a next-generation probiotic.

Multifocal osteonecrosis due to the synergistic impact of inherited thrombophilia, autoimmunity, and pregnancy: A case report.

Multifocal osteonecrosis is a rare entity which can lead to bone fragility, fractures, and considerable morbidity. The objective of this report is to describe the presentation, evaluation, and management of a case of multifocal osteonecrosis. A 34-year-old lady presented with multiple fractures and bone pain which was exacerbated during pregnancy. She was found to have osteonecrosis involving multiple sites. Investigation revealed that she had an undefined autoimmune condition with antinuclear antibody and anti-Ro (SS-A) positivity, not fulfilling criteria for diagnosis of Sjogren syndrome. She had low Protein S (PS) levels for age and gender (confirmed on two occasions 12 weeks apart outside pregnancy). She had a novel variant in the PROS1 gene (NM_000313.4:c.1513 G > A; p.Gly505Ser) which is associated with heterozygous PS deficiency. She had a good response to treatment with anticoagulation. The combination of inherited thrombophilia, autoimmunity, and the thrombophilic state induced by pregnancy probably contributed to the severe phenotype in this patient. The variant was identified in the Lamin G1 domain, which is instrumental in PS binding to tissue factor pathway inhibitor and C4-binding protein, thus playing a role in both the coagulation and complement pathway, and could explain the coexistence of autoimmunity with thrombophilia. This variant is present in 0.034% of South Asians in the gnomAD population database, and may represent an important cause of inherited thrombophilia in this group.

Mortality in Patients With Sjögren Disease: A Prospective Cohort Study Identifying Key Predictors.

We aimed to quantify the mortality risk in a large, well-characterized cohort of patients with Sjögren disease (SjD) and to identify independent predictors of mortality in this population. We included 314 patients diagnosed with SjD according to the 2002 American-European Consensus Group criteria from a prospective, multicenter SjögrenSER Prospective cohort. Detailed data on systemic manifestations, serological markers, disease activity, and mortality were collected after a median of 9.5 (IQR 9.2-9.9) years of follow-up. The primary outcome was overall mortality, and secondary analyses aimed to identify independent predictors of mortality using Cox proportional hazards models. Standardized mortality ratios were calculated by comparing the observed deaths in the SjD cohort to the expected deaths in an age- and sex-matched general population. The study identified a 70% increased mortality risk in the SjD cohort compared to the general population, with a standard mortality ratio of 1.7. Infections (35.7%), malignancies (23.8%), and cardiovascular disease (CVD; 7.1%) were the most common causes of death. Multivariate analysis revealed that older age (HR 1.11/year, 95% CI 1.07-1.15), C4 hypocomplementemia (HR 3.75, 95% CI 1.55-9.06), elevated erythrocyte sedimentation rate (ESR; HR 1.01, 95% CI 1.00-1.03), history of heart failure (HR 4.24, 95% CI 1.02-17.58), and pulmonary involvement (HR 3.31, 95% CI 1.39-7.88) were independent predictors of mortality. This study found a significantly increased mortality risk in SjD, with infections, malignancies, and CVD as leading causes of death. Independent predictors of mortality include advanced age, C4 hypocomplementemia, elevated ESR, heart failure, and pulmonary involvement, underscoring the need for proactive, individualized management.

Late-onset Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune rheumatic disease (ARD) that results from the dysregulation of multiple innate and adaptive immune pathways. Late-onset SLE (Lo-SLE) is the term used when the disease is first diagnosed after 50-65 years, though the standard age cut-off remains undefined. Defining "late-onset" as lupus with onset after 50 years is more biologically plausible as this roughly corresponds to the age of menopause. Lo-SLE comprises nearly 20% of all cases of lupus. With advancing age, the female predominance of lupus declines to nearly 4:1 to even 1.1:1. The natural history of the disease varies, with lesser major organ involvement like nephritis but higher damage accrual. The latter is possibly owed to the atypical presentation and hesitation among physicians to diagnose SLE at this age, a diagnostic delay with late treatment initiation may accelerate the damage accrual. Multimorbidity is a central issue in these patients, which includes osteoporosis, sarcopenia, accelerated atherosclerosis in the background of existing dyslipidemia, diabetes mellitus, major depression, hypertension, coronary artery disease and other thrombotic events.With the rising ages of populations worldwide, awareness about late-onset lupus is paramount, especially due to the associated diagnostic delays and higher overlap with Sjogren's disease. Also, pharmacotherapeutics must be optimized considering factors associated with ageing like declining glomerular filtration rate (GFR), sarcopenia, osteoporosis, and the associated comorbidities. Measures to minimize the exposure to long-term exposure to high-dose steroids are crucial. Beyond this, it is of essence to adopt non-pharmacological interventions as an adjunct to traditional immunosuppression to improve pain, fatigue, depression, and anxiety, improve cardiovascular health and overall better quality of life with favourable long-term outcomes.

The Effect of Autologous Serum Tears 50% on the Ocular Surface of Patients With Severe Dry Eye Disease due to Sjogren Syndrome: A Prospective, Double-Blind, Randomized, Controlled, Contralateral Eye Study.

To assess the impact of autologous serum (AS) tears at a 50% concentration on the ocular surface of patients with refractory dry eye disease (DED) because of Sjogren syndrome. Twenty eyes of ten patients with severe immune-mediated DED were contralaterally randomized to receive either AS tears 50% or artificial tears between June 2021 and May 2023. Changes in tear stability, ocular surface staining, and in the morphology of the corneal sub-basal nerves were evaluated before treatment and at 1, 2, and 3 months after treatment using objective tests for DED and confocal microscopy. The microbiological safety of the used AS tears 50% was investigated using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. The AS tears 50% group exhibited significant improvements in tear break-up time, Schirmer test scores, visual acuity, and confocal microscopy parameters of corneal nerve health at the 3-month follow-up (P < 0.05). Corneal nerve regeneration correlated with increased tear stability and decreased ocular surface staining. Microbiological analysis identified Gram-negative bacteria in the postuse AS tears, highlighting the need for meticulous handling and storage practices. Treatment with AS tears at a 50% concentration markedly enhances ocular surface health, tear stability, and visual acuity, affirming the regenerative effects on corneal nerves in severe DED. The findings advocate for the therapeutic potential of higher-concentration AS tears in DED management, albeit with strict protocols to mitigate contamination risks and ensure patient safety.

Genetic insight into dissecting the immunophenotypes and inflammatory profiles in the pathogenesis of Sjogren syndrome

BackgroundSjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells and inflammatory factors. Despite increased researches and studies recently focusing on this area, it remains to be fully elucidated. We decide to incorporate genetic insight into investigation of the causal link between various immune cells, inflammatory factors and pathogenesis of Sjogren syndrome (SS).MethodsOur study leveraged the genetic variants of multi-omics statistics extracted from genome-wide association study (GWAS), the University of Bristol and the FinnGen study. We performed a bidirectional Mendelian randomization and mediation study based on randomly allocated instrumental variables to infer causality, followed by external validation with UK Biobank data and Bayesian colocalization.ResultsWe demonstrated that an elevated level of CD27 on IgD + CD24 + B cell, a subset of B cells expressing both IgD and CD24, was associated with a higher risk of SS (OR = 1.119, 95% CI: 1.061–1.179, P < 0.001), while CD3 on CD45RA + CD4 + Treg was a protective factor (OR = 0.917, 95%CI: 0.877–0.959, P < 0.001). Results of meta-analysis and colocalization further supported the significant results identified in the primary analysis. A total of 4 inflammatory cytokines and 7 circulating proteins exhibited potential causal relationships with SS despite no significant result achieved after FDR correction. Finally, results of mediation analysis indicated that CD40L receptor levels had significant mediating effects (β = 0.0314, 95% CI: 0.0004–0.0624, P = 0.0471) at a mediation proportion of 28% (95% CI: 0.364%-55.6%) in causal relationship between CD27 on IgD + CD24 + B cell and SS.ConclusionsBy providing a novel genetic insight into unveiling the roles of autoimmunity and inflammation in Sjogren syndrome, our findings may potentially lead to identifying new clinical biomarkers for disease monitoring and therapeutic targets that offer more effective alternatives for treating this condition. Therefore, our study may provide valuable evidence for future clinical intervention and targeted immunotherapy.

SHED-Derived Exosomes Ameliorate Sjögren's Syndrome-Induced Hyposalivation by Suppressing Th1 Cell Response via the miR-29a-3p/T-bet Axis.

Background: Sjögren's syndrome (SS), an autoimmune disease, was characterized by sicca syndrome and systemic manifestations, presenting significant treatment challenges. Exosomes, naturally derived nanoparticles containing bioactive molecules, have garnered interest in regenerative medicine. The present study aimed to elucidate the immunoregulatory properties and mechanism of exosomes obtained from the stem cells derived from human exfoliated deciduous teeth (SHED-exos) in SS-induced sialadenitis. Methods: SHED-exo nanoparticles were injected into submandibular glands (SMGs) of 14-week-old nonobese diabetic (NOD) mice, a classic animal model of SS. At 21 weeks, the saliva flow rate (SFR) was measured. Lymphocyte proportions were examined via flow cytometry. Inflammatory cytokine levels were examined by the Quantibody mouse Th1/Th2/Th17 array and ELISA. miR-29a-3p expression and its regulatory effect on T-bet was detected using FISH and luciferase reporter gene assay, respectively. Results: SHED-exos injected into SMGs increased SFR, reduced lymphocytic infiltration, and decreased inflammatory cytokine levels in serum, SMG tissues, and saliva. Mechanistically, SHED-exos suppressed the Th1 proportion in spleen lymphocytes in NOD mice. Exosomal miR-29a-3p targeted and suppressed T-bet expression, which is a Th1-specific transcription factor. In vitro, SHED-exos (but not miR-29a-3p-inhibited exosomes) decreased the level of Th1 differentiation and IFN-γ and TNF-α production. Furthermore, SHED-exos (but not miR-29a-3p-inhibited exosomes) blocked the increase in IFN-γ and TNF-α production induced by T-bet overexpression. In vivo, miR-29a-3p-inhibited exosomes neither increase saliva secretion in NOD mice nor decrease lymphocytic infiltration, T-bet expression, and IFN-γ and TNF-α levels in SMGs. Conclusion: SHED-exos suppress Th1 cell differentiation and response through the miR-29a-3p/T-bet axis, contributing to amelioration of SS-induced hyposalivation.