Treatment Of Sjogren's Syndrome Research Articles

Chemokines and lymphocyte homing in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease that typically presents with lymphocyte, dendritic cell, and macrophage infiltration of exocrine gland ducts and the formation of ectopic germinal centers. The interactions of lymphocyte homing receptors and addressins and chemokines and their receptors, such as α4β7/MAdCAM-1, LFA-1/ICAM-1, CXCL13/CXCR5, CCL25/CCR9, CX3CL1/CX3CR1, play important roles in the migration of inflammatory cells to the focal glands and the promotion of ectopic germinal center formation in SS. A variety of molecules have been shown to be involved in lymphocyte homing, including tumor necrosis factor-α, interferon (IFN)-α, IFN-β, and B cell activating factor. This process mainly involves the Janus kinase-signal transducer and activator of transcription signaling pathway, lymphotoxin-β receptor pathway, and nuclear factor-κB signaling pathway. These findings have led to the development of antibodies to cell adhesion molecules, antagonists of chemokines and their receptors, compounds interfering with chemokine receptor signaling, and gene therapies targeting chemokines and their receptors, providing new targets for the treatment of SS in humans. The aim of this study was to explore the relationship between lymphocyte homing and the pathogenesis of SS, and to provide a review of recent studies addressing lymphocyte homing in targeted therapy for SS.

Rutin alleviates Sjogren's syndrome via CaR/NLRP3/NF-κB signal pathway.

Sjogren's syndrome (SS) is an autoimmune disease. Its mechanism and treatment methods are unclear. The purpose of this study was to investigate the effects of rutin (Ru) on SS. Proteomics was used to detect differential proteins in the submandibular glands of normal mice and SS mice. Salivary secretion (SAS) and salivary gland index (SGI) were detected. Oxidative stress and inflammatory cytokine in submandibular glands were detected. The levels of NLRP3, ASC, Caspase-1, IL-1β, and p-NF-κBp65 in submandibular gland tissues and submandibular gland cells of overexpressedcalcium-sensing receptor (over-CaR) mice and overexpressed CaR primary submandibular gland cells (over-CaR-PSGs) were detected. In total, 327 differential proteins were identified in the submandibular gland tissues of SS mice compared to control mice. CaR was one of the most differential proteins and significantly increased compared to control mice. Ru could significantly increase SGI and SGI, and inhibit oxidative stress and inflammatory cytokine in submandibular glands. In addition, Ru was shown to further improve SS via regulation of the CaR/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/nuclear factor kappa-B (NF-κB) signal pathway. Overexpression of CaR counteracted partial activity of Ru. CaR may be an important target for the treatment of SS. In addition, Ru improved the SS via the CaR/NLRP3/NF-κB signal pathway. This study provides a basis for the treatments for SS.

Network pharmacology and molecular docking analysis on the mechanism of Tripterygium wilfordii Hook in the treatment of Sjögren syndrome.

Tripterygium wilfordii Hook. F (TWH) has significant anti-inflammatory and immunosuppressive effects, and is widely used in the inflammatory response mediated by autoimmune diseases. However, the multi-target mechanism of TWH action in Sjögren syndrome (SS) remains unclear. Therefore, the aim of this study was to explore the molecular mechanism of TWH in the treatment of SS using network pharmacology and molecular docking methods. TWH active components and target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. SS-related targets were obtained from the GeneCards database. After overlap, the therapeutic targets of TWH in the treatment of SS were screened. Protein-protein interaction and core target analysis were performed by STRING network platform and Cytoscape software. In addition, the affinity between TWH and the disease target was confirmed by molecular docking. Finally, the DAVID (visualization and integrated) database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of overlapping targets. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database shows that TWH contains 30 active components for the treatment of SS. Protein-protein interaction and core target analysis suggested that TNF, MMP9, TGFB1, AKT1, and BCL2 were the key targets of TWH in the treatment of SS. In addition, the molecular docking method confirmed that the bioactive molecules of TWH had a high affinity with the target of SS. Enrichment analysis showed that TWH active components were involved in multiple signaling pathways. Pathways in cancer, Lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications is the main pathway. It is associated with a variety of biological processes such as inflammation, apoptosis, immune injury, and cancer. Based on data mining network pharmacology, and molecular docking method validation, TWH is likely to be a promising candidate for the treatment of SS drug, but still need to be further verified experiment.

Integrated analysis of m6A regulator-mediated RNA methylation modification patterns and immune characteristics in Sjögren's syndrome

The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.

Total glucosides of paeony alleviates experimental Sjögren's syndrome through inhibiting NLRP3 inflammasome activation of submandibular gland cells.

The mechanisms by which total glucosides of paeony (TGP) mitigates Sjögren's syndrome (SS) remains elusive. In the present study, we aim to explore the relationship between the therapeutic effects of TGP in the treatment of SS and NLRP3 inflammasome activation in submandibular gland (SG) cells. Female non-obese diabetic (NOD) mice were selected as the model of SS. The mice were divided into PBS and TGP treatment group. For treatment, TGP (400mg·kg-1) was administered intragastrically every day for 4 weeks. The SS-like symptoms and pathological changes of the SG of mice were compared between the PBS and TGP group. The activation of NLRP3 inflammasome in SG was detected by RT-qPCR, immunohistochemistry and western blot. The SG cells stimulated by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) for activation of NLRP3 inflammasome were treated with or without TGP. Then, NLRP3 inflammasome activation was assessed. The IL-1β and IL-18 in homogenate of SG, serum and supernatant were detected by ELISA. Compared with balb/c mice, NOD mice showed SS-like symptoms and lymphocyte infiltration in SG, and the expression of NLRP3 inflammasome in SG was significantly increased. The SS-like symptoms were alleviated, and lymphocyte infiltration in SG was reduced, and the level of NLRP3 inflammasome in SG mice was decreased after TGP treatment. TGP also significantly inhibit the activation of NLRP3 inflammasome of SG cells in vitro. Collectively, our results indicated that TGP alleviates SS through inhibition of the activation of NLRP3 inflammasome of SG. These findings clarified the mechanism underlying the therapeutic effects of TGP on SS, and provided new evidence for the further application of TGP in the treatment of SS.

Clinical practice guidelines for the treatment of primary Sjögren's syndrome by off-label drug use in China(2023 edition)

Sjögren's syndrome (SjS) is one of the most prevalent rheumatic diseases. Off-label drug use is very common in the clinical practice of the treatment of SjS. In order to establish evidence-based justifications and systematically evaluate the off-label drug use in SjS treatment, the Committee of Chinese Primary Health Care Foundation for Rheumatologists and Immunologists referred to published guidelines, consensus statements, and case series, and reevaluated the outcomes of the randomized controlled trials about the marketed immunosuppressive drugs treating SjS. The single-item breakdown of the Sjögren's tool for assessing response (STAR) which was proposed in 2022 was employed as the outcome. The committee established the corresponding clinical questions based on the population, intervention, comparison, and outcome (PICO) principle, and then carried out evidence retrieval, and synthesized meta-analysis using the grading of recommendations, assessment, development, and evaluation (GRADE) methodology. Finally, 21 recommendations addressing twelve clinical questions were formed which included two strong recommendations, fourteen weak recommendations, and five consensus-based recommendations. The overarching objective of the guideline is to provide clinicians with a rational basis for medication selection and to offer guidance to pharmacy departments for management purposes.

Recommendations for the diagnosis and treatment of Sjögren's syndrome in China

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocyte proliferation and progressive exocrine gland damage. In addition to the impairment of salivary and lacrimal gland function, SS can present with multi-system and multi-organ involvement, accompanied by autoantibodies in serum and hyperimmunoglobulinemia. SS can be divided into primary and secondary forms based on the absence or presence, respectively, of concurrent connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis. Based on evidence and guidelines from China and other countries, the Chinese Rheumatology Association drafted standardized criteria for the diagnosis and treatment of primary SS. The objectives were to standardize the detection and interpretation of key indicators for the diagnosis of SS, including serum anti-SSA antibody and labial gland pathology, suggest the use of the widely accepted European League Against Rheumatism (EULAR)-SS disease activity index for the evaluation of the disease, and standardize the rational management of SS patients with topical and systemic therapies.

Inhibition of CD4 + T cells by fanchinoline via miR506-3p/NFATc1 in Sjögren's syndrome.

The hyperproliferation and hyperactivation of CD4 + T cells in salivary gland tissues are hallmarks of Sjögren's syndrome (SS). Fangchinoline (Fan) is extracted from the root of Stephania tetrandra Moore, which is used for treating rheumatic diseases in many studies. This study aimed to identify the mechanism underlying the inhibition of CD4 + T cells by Fan in the SS model NOD/ShiLtj mice. In vivo, Fan alleviated the dry mouth and lymphocyte infiltration in the salivary gland tissues of the NOD/ShiLtj mice and inhibited the number of CD4 + T cells in the infiltrating focus. In vitro, Fan's inhibitory effect on the proliferation of mouse primary CD4 + T cells was verified by CFSE and EdU tests. Furthermore, qRT-PCR and WB analysis confirmed that Fan could inhibit the expression of NFATc1 (Nuclear factor of activated T-cells, cytoplasmic 1) by upregulating miR-506-3p. Dual luciferase reporter gene assay suggested that miR-506-3p interacted with NFATc1. CFSE and EdU tests showed that Fan could inhibit the proliferation of CD4 + T cells through miR-506-3p/NFATc1. The key role of NFATc1 in the activation of CD4 + T cells and the high expression of NFATc1 in samples from SS patients suggested that NFATc1 might become a therapeutic target for SS. In vivo, 11R-VIVIT (NFATc1 inhibitor) alleviated SS-like symptoms. This study not only explained the new mechanism of Fan inhibiting proliferation of CD4 + T cells and alleviating SS-like symptoms but also provided NFATc1 as a potential target for the subsequent research and treatment of SS.

Targets of total glucosides of paeony in the treatment of Sjogren syndrome: A network pharmacology study.

We aimed to explore the underlying mechanism of the total glucoside of peony (TGP) in treating Sjogren syndrome (SS) using the network pharmacology approach. The protein targets of TGP and SS were identified by database search. Then, the intersection of the two groups was studied. The drug-target network between TGP and the overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment were performed to analyze these genes. Finally, the predictions of potential targets were evaluated by docking study. Forty-six overlapping genes were discovered. The results suggested that TGP used in the treatment of SS is associated with cellular tumor antigen p53, neurotrophic tyrosine kinase receptor type 1, and epidermal growth factor receptor, as well as their related 3372 protein networks, which regulate intrinsic apoptotic signaling pathway, cellular response to oxidative stress, rhythmic process, and other processes. Molecular docking analysis proved that hydrogen bonding is the main form of interaction. Our research provided the protein targets affected by TGP in SS treatment. The key targets (caspase 3, vascular endothelial growth factor A, glyceraldehyde-3-phosphate dehydrogenase, etc.), which involve 3372 proteins, are the multitarget mechanism of TGP in SS treatment.

Сочетание синдрома Шегрена и тромботической тромбоцитопенической пурпуры

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a disease caused by the formation of antibodies to the ADAMTS13 enzyme. Sjogren's syndrome (SS) is also an autoimmune disease, but the mutual effect on the prognosis and treatment of iTTP and SS is not clear. We present the clinical case and the review to determine the mutual effects of SS and iTTP. We conducted the literature review including all PubMed/MEDLINE articles found using the terms "Sjogren's syndrome" and "thrombocytopenic purpura". The review of the literature demonstrates the lower effectiveness of TPE monotherapy compared to TPE + ISD as a first-line therapy. Perhaps in the future it is necessary to consider the possibility of an earlier appointment of ISD in patients with a combination of SS and iTTP. Key words: Sjogren's syndrome, dry syndrome, thrombotic thrombocytopenic purpura, thrombotic microangiopathy, ADAMTS13

Sjögren's Syndrome Treatments in the Microbiome Era.

Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by inflammatory cell infiltration of the salivary and lacrimal glands, resulting in acinar epithelial cell atrophy, cell death, and loss of exocrine function. At least half of SS patients develop extraglandular inflammatory disease and have a wide range of systemic clinical manifestations that can affect any organ system, including connective tissues. As many as 3.1 million people in the U.S. suffer from SS, a disease that causes severe impairment. Women are nine times more likely than men to be affected by this condition. Unfortunately, there is currently no effective treatment for SS, and the available options only provide partial relief. Treatment involves using replacement therapies such as artificial saliva and eye lubricants, or immunosuppressive agents that have limited efficacy. The medical community recognizes that there is a significant need for more effective treatments for SS. Increasing evidence demonstrates the links between the dysfunction of the human microbial community and the onset and development of many human diseases, signifying the potential use of microorganisms as an alternative strategy to conquer these issues. The role of the microbiome in controlling immune function of the human host in the context of autoimmune diseases like SS is now becoming better understood and may help to enable new drug development strategies. Natural probiotics and synthetic biology applications hold promise for novel treatment approaches to solve the encryption of many complex and multifactorial immune disorders, like SS.

Fangchinoline Inhibited Proliferation of Neoplastic B-lymphoid Cells and Alleviated Sjögren's Syndrome-like Responses in NOD/Ltj Mice via the Akt/mTOR Pathway.

Fangchinoline is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra S. Moore that is conventionally used as an analgesic, antirheumatic, and antihypertensive drug in China. However, the application of Fanchinoline in Sjögren syndrome (SS) remains unreported. This study aimed to identify the potential role of Fangchinoline in the treatment of SS via altering Akt/mTOR signaling. First, we examined levels of p-Akt and p-mTOR in infiltrating lymphocytes of labial glands from SS patients by immunohistochemistry. Then, the effects of Fangchinoline on Raji cells and Daudi cells were investigated using the CCK-8 assay, propidium iodide (PI)/RNase, and Annexin V/PI staining. Western blotting was used to identify the levels of Akt, p-Akt(ser473), mTOR, and p-mTOR. For in vivo analyses, NOD/Ltj and wild-type ICR mice were treated with a Fangchinoline solution, an LY294002 solution (an inhibitor of the PI3K/Akt/mTOR pathway), or their solvent for 28 days. Then, salivary flow assays and hematoxylin and eosin staining of submandibular glands were performed to determine the severity of SS-like responses in the mice. Immunohistochemical staining of labial glands from SS patients showed that activation of p-Akt and p-mTOR in infiltrating lymphocytes might be correlated with SS development. In vitro, Fangchinoline and LY294002 inhibited proliferation, induced cell cycle arrest, and promoted apoptosis in Raji and Daudi cells by altering Akt/mTOR signaling. In vivo, Fangchinoline and LY294002 significantly improved the salivary secretion by NOD/Ltj mice and reduced the number of lymphocytic foci in the submandibular glands. These results indicated that Fangchinoline could effectively inhibit the proliferation of neoplastic B-lymphoid cells and reduce SS-like responses in NOD/Ltj mice. Our study highlights the potential value of the clinical application of Fangchinoline for SS treatment.

Targeting EZH2 prevents the occurrence and mitigates the development of Sjögren's syndrome in mice

ObjectiveWe analyzed RNA-SEQ data and found that EZH2 gene expression in salivary glands (SGs) of Sjögren's syndrome (SS) patients was up-regulated and correlated with pathological injury. In this study, we sought to determine if inhibiting EZH2 would ameliorate SS-like disease in NOD/Ltj (NOD) mice. MethodsWe analyzed RNA-SEQ data of SGs of patients with SS from data obtained from the GEO database to explore the correlation between EZH2 gene expression and the progression of SS. Inhibition of EZH2 in the NOD mice was achieved by intraperitoneal administration of GSK343 using both a preventative and a therapeutic model. The effects of GSK343 on SGs secretion and pathological damage, as well as the levels and functions of T cells, B cells, Myeloid-derived suppressor cells (MDSCs), and other immune cells were evaluated. ResultsThe expression levels of the gene encoding EZH2 in the SGs of SS patients were significantly higher than the non-SS sicca patients, and the expression levels were positively correlated with the severity of the SGs pathological damage. GSK343 treatment significantly increased the salivary flow rate and pathological damage of the SGs in the NOD mice compared to the control mice. In addition, GSK343 significantly inhibited the number and pro-inflammatory-factor secretion of CD4+ and CD8+ T cells and inhibited the increase in the Th1/Th2 cell ratio caused by SS. RNA-SEQ data also showed that EZH2 inhibited several inflammatory pathways during the pathogenesis of SS. ConclusionsEZH2 expression was up-regulated in the submandibular gland tissue of SS patients.Inhibition of EZH2 alleviated SS-like disease in NOD mice, suggesting that EZH2 might be a potential target for the clinical treatment of SS.

Umbilical cord mesenchymal stem cells alleviate Sjögren's syndrome and related pulmonary inflammation through regulating Vγ4+ IL-17+ T cells.

BackgroundSince gamma delta (γδ) T cells are involved in various autoimmune diseases, we aimed to verify whether γδ T cells participate in the pathogenesis of Sjögren’s syndrome (SS) and related pulmonary inflammation, and also aimed to evaluate the effects of umbilical cord mesenchymal stem cells (MSCs) on SS-related pulmonary inflammation and the γδ T cells.MethodsThe saliva flow rates of female non-obese diabetic (NOD/Ltj) mice were measured. Histopathologic analysis was performed in salivary glands (SG) and lung tissues. The levels of γδ T cells and their subsets in the peripheral blood, spleen, and lung were examined by flow cytometry. The purified γδ T cells were adoptively transferred into NOD/Ltj mice. MSC transplantation was performed in 8-week-old NOD/Ltj mice.ResultsThe results showed lymphocytic infiltration in SG and lacrimal glands (LG), and reduction of saliva flow rates in 8-week NOD/Ltj mice. The levels of γδ T cells decreased in peripheral blood, but increased in the lung of 8- and 12-week-old NOD/Ltj mice. The proportions and numbers of Vγ4+ T cells and Vγ4+ IL-17A+ T cells increased in the lung, but decreased in peripheral blood of 8-week-old NOD/Ltj mice. Notably, transfer of γδ T cells decreased the rate of saliva flow, as well as aggravated the pathological changes in the lung. The transplantation of MSCs increased saliva flow rate and alleviated pathological injury in the SG and lung. The frequencies of Vγ4+ T cells and Vγ4+ IL-17A+ T cells in the lung and spleen significantly decreased after MSC treatment. Our results demonstrated that γδ T cells and Vγ4+ T cells contribute to the pathogenesis of SS and SS-related pulmonary inflammation. In addition, MSCs relieved SS and SS-related pulmonary inflammation through suppressing Vγ4+ IL-17A+ T cells.ConclusionsPeripheral Vγ4+ T cells infiltrate into the lung in SS mice, and aggravate the symptoms of SS and SS-related pulmonary inflammation by secreting IL-17A. Meanwhile, lymphocyte infiltration could be reversed by MSC transplantation, which indicates the potential of MSCs in the treatment of SS and SS-related pulmonary inflammation patients.

Tetrahedral Framework Nucleic Acids Reestablish Immune Tolerance and Restore Saliva Secretion in a Sjögren's Syndrome Mouse Model.

As one of the most frequent autoimmune diseases, Sjogren's syndrome (SS) is characterized by overactive lymphocytic infiltration in the exocrine glands, with ensuing dry mouth and dry eyes. Unfortunately, so far, there are no appropriate therapies without causing overall immunosuppression. Tetrahedral framework nucleic acids (tFNAs) were regarded as promising nanoscale materials whose immunomodulatory capabilities have already been verified. Herein, we reveal, for the first time, that tFNAs were utilized to treat SS in female nonobese diabetic (NOD) mice, the animal model used for SS. We proved a 250 nM tFNA treatment was successful in suppressing inflammation and stimulating saliva secretion in NOD mice. Specialised proteins for the secretory function and structure of acinar cells in submandibular glands (SMGs) were restored. It has been the permanent goal for SS treatment to establish immune tolerance and stop disease development. Surprisingly, tFNA treatment guided T cells toward regulatory T cells (Tregs), while suppressing T helper (Th) cell responses. Th cells include Th1, Th17, and follicular helper T (Tfh) cells. Tregs are highly significant in immune tolerance. Inducing Tregs is a promising approach to reestablish immune tolerance. Comparable results were also observed in B cell responses. Reductions in the percentage of germinal center (GC) B cells and plasma cells were detected, and a marked increase in the percentage of regulatory B cells (Bregs) was also noticed. The mechanisms of inducing Tregs may associated with cytokine changes. Changes of T cell subsets, especially changes of Tfh, may influence the differentiation of B cells accordingly. Collectively, our results demonstrated the immunomodulatory capacities of tFNAs once again, which may provide a novel, safe, and effective option for the treatment of SS and other autoimmune diseases.

Efficacy and safety of Tripterygium glycosides in Sjögren's syndrome treatment: evidence from 12 randomized controlled trials.

Tripterygium glycosides (TGs) has been widely used in the treatment of Sjögren's syndrome (SS). Seven databases, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Medical Database, China Science and Technology Journal Database, and the Chinese Biomedicine database, were selected to collect randomized controlled trials (RCTs) related to the treatment of SS with TGs alone or in combination. The participants, intervention, comparison, outcome, and study design principle were adopted for the inclusion of related studies. The risk of bias was assessed using the Cochrane Collaboration's tool. Meta-analysis was conducted using RevMan 5.3, with risk ratios (RRs) or standard mean differences (SMDs) and 95% confidence intervals (CIs). Overall, 12 trials involving 668 patients were analyzed. The results of the meta-analysis showed that TGs in combination with total glucosides of paeony (TGP) had significantly lower symptom scores than TGs alone on dry eyes (SMD =-0.61, 95% CI: -1.12 to -0.10, P=0.02) or dry mouth (SMD =-1.29, 95% CI: -1.84 to -0.74, P<0.00001). The efficacy rates of TG + TGP vs. TGs (P<0.00001) and TG + HM vs. TGs (P=0.01) were significantly different. In addition, compared to hydroxychloroquine (HCQ), TGs could induce expression of C-reactive protein (P=0.007), globulin (P<0.00001), and immunoglobulin A (IgA) (P=0.006), whereas the TG + TGP group had lower levels of immunoglobulin G (IgG) (P<0.00001), immunoglobulin M (IgM) (P=0.02), and IgA (P<0.00001), as well as saliva flow rate (P<0.00001) and lacrimal gland function (P<0.00001). The adverse events between TGs and HCQ were not evident, and there was no increase in the risk of adverse reactions when combined with other drugs. TGs are potentially effective for treating SS without increasing the risk of adverse events. High-quality, multi-center, and large-scale RCTs are required.

Protective effects of miR-155-5p silencing on IFN-γ-induced apoptosis and inflammation in salivary gland epithelial cells.

Previous studies have demonstrated that microRNAs (miRNAs/miRs) serve a vital role in the pathogenesis of Sjögren's syndrome (SS). The present study aimed to investigate the role of miR-155-5p in SS and determine its underlying molecular mechanism. An inflammatory lesion model was established by stimulating salivary gland epithelial cells (SGECs) with interferon-γ (IFN-γ). The apoptosis of SGECs was measured by using flow cytometry. Levels of proinflammatory factors were detected by reverse transcription-quantitative PCR and ELISA, respectively. Immunofluorescence was used for p65 staining. Dual-luciferase reporter assay was performed to verify the interaction between miR-155-5p and arrestin β2 (ARRB2). The protein levels in the NF-κB signaling pathway were assessed by western blotting. The results of the present study demonstrated that treatment with IFN-γ increased miR-155-5p expression, in addition to inducing apoptosis and inflammation in SGECs. Furthermore, overexpression of miR-155-5p promoted IFN-γ-induced apoptosis and inflammation in SGECs. Overexpression of miR-155-5p also increased Bax protein expression, enzyme activities of caspase 3 and caspase 9, release of inflammatory cytokines interleukin-6 and tumor necrosis factor-α, and decreased Bcl-2 protein expression in IFN-γ-treated SGECs. By contrast, all of the effects aforementioned were reversed following miR-155-5p knockdown. These results demonstrated that miR-155-5p activated the NF-κB signaling pathway, where treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate, reversed the effects of miR-155-5p overexpression on the inflammatory factors in IFN-γ-induced SGECs. miR-155-5p was demonstrated to target ARRB2 and negatively regulated its expression levels, such that overexpression of ARRB2 reversed the effects of miR-155-5p overexpression on the inflammatory response, apoptosis and the NF-κB signaling pathway in IFN-γ-treated SGECs. Collectively, results from the present study suggest that miR-155-5p may activate the NF-κB signaling pathway by negatively regulating ARRB2 to promote salivary gland damage during SS pathogenesis. This suggests that miR-155-5p may serve to be a potential target for the treatment of SS.

Coexistence of Sjögren syndrome in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: A retrospective observational study.

To identify the prevalence and clinical characteristics of Sjögren syndrome (SS) in a Chinese single-center cohort of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.Patients diagnosed with SS were screened out from a cohort of 164 cases of SAHPO syndrome. Information regarding the patients’ gender, age at onset, clinical features, laboratory tests, bone scintigraphy, and treatment was reviewed.Five patients were screened out. The prevalence of SS in SAPHO patients was 3.05% The mean onset age of SS was 48.0 ± 12.0 years old and no apparent time order in the occurrence of SAPHO and SS was observed. Compared with the general SAPHO cohort, the 5 SS patients exhibited no significant difference in the SAPHO related clinical features or inflammatory markers, except for a higher prevalence of peripheral joints and bones involvement in bone scintigraphy. Objective evidence of dryness and positive salivary gland biopsy were found in all the patients. However, the positive rates of SSA and SSB antibody were only 20%. Anti-inflammatory treatment for SS was recorded in 3 patients (ESSDAI score: 3 in 2 patients; 12 in 1 patient) with extra-glandular manifestations, severe complications or poor response to the basic treatment.The prevalence of SS is higher in the SAPHO cohort than in the general Chinese population. Objective tests or biopsy might be more indicative than the antibody detection for SS diagnosis. Anti-inflammatory treatment should be prescribed in consideration of both the severity of SS and the demand for disease activity control of SAPHO.

Early diagnosis and treatment for Sjögren's syndrome: current challenges, redefined disease stages and future prospects.

There are some challenges and unmet needs in the early diagnosis and management of Sjögren's syndrome (SjS) such as prominent glandular dysfunction at diagnosis and long diagnostic delay. Those challenges are partly attributed to the lack of a good knowledge of the early stages of SjS, which is a major obstacle to delivering appropriate care to SjS patients. Findings from both clinical and experimental studies suggest the plausibility of a redefined SjS course consisting of 4 stages, which includes initiation stage, preclinical stage, asymptomatic SjS stage and overt SjS stage. More studies focusing on the pathological processes and changes during the early stages of SjS are needed. To enable early diagnosis and treatment for SjS, more useful biomarkers of the early stages of SjS need to be identified, and individuals at high risk of SjS development need to be identified. Appropriate screening can be performed to facilitate the early diagnosis of SjS among those high-risk individuals.

Biologic therapy in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease with complex and diverse clinical manifestations. It is characterized by lymphocyte infiltration of exocrine glands such as the salivary gland and lacrimal gland leading to insufficient secretion of the gland, manifested as dry mouth and dry eyes. In addition, it can involve extraglandular organs and cause systemic damage. The pathogenesis of SS is still unclear. At present, symptomatic treatment is the mainstay and there is a lack of effective therapy. With the development of molecular pathways underlying the pathogenesis of SS, more and more novel biological agents are used to treat SS. We summarized and analyzed the existing evidences on the efficacy of biological treatment of SS and their targets. Analysis of the efficacy of biological therapy and improvement of treatment strategies can help to give full play to its therapeutic advantages.