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Objective: This study aimed to compare the salivary gland ultrasonography(SGUS) findings in patients with primary Sjögren's Syndrome (pSS) and diabetes mellitus(DM) patients with sicca symptoms and to examine the relationship between salivary gland ultrasonography (SGUS) findings with clinical and laboratory parameters. Methods: In this study, 34 patients with pSS and 34 DM patients with sicca symptoms were included. In all patients, bilateral parotid, and submandibular gland ultrasonography (totally 272 glands) was performed by blinded rheumatologist, using the Hocevar and the Outcome Measures in Rheumatology (OMERACT) scoring system. Clinic and ultrasonographic variables were compared between groups. The association between SGUS score and disease duration was analyzed by correlation analysis. Results: Patients with pSS presented significantly higher SGUS scores than patients with DM (the Hocevar score; 20.93(± 9.65) vs. 3.82(± 3.71); p < 0.05, the OMERACT score; 5.96(± 2.30) vs. 2.07(± 1.65); p < 0.05, respectively). In patients with pSS, the submandibular gland scores were significantly higher than the parotid gland scores (right; p < 0.05 vs. left; p < 0.01) while DM patients showed significantly higher parotid gland scores (right; p < 0.05 vs. left; p < 0.05). In pSS patients, the SGUS scores were associated with disease duration (r = 0.57; r = 0.50; p < 0.05), symptom duration (r = 50; r = 0.47; p < 0.05), and the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index (ESSPRI)-dryness score (r = 0.35, r = 0.36; p < 0.05). However, in DM patients, the SGUS scores are highly correlated with the ESSPRI-dryness (r = 0.74, r = 0.72; p < 0.05) and HbA1C level (r = 0.91, r = 0.86; p < 0.05). Conclusions: This study demonstrated that major salivary gland involvement was more severe and correlated with disease duration, and submandibular gland was dominantly affected in pSS. Contrarily, in DM patients, salivary gland involvement was milder, parotid dominant and related to level of dryness and HbA1C, rather than disease duration when compared to pSS, [ABSTRACT FROM AUTHOR]

Background: Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms. Case presentation: We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms. Conclusion: This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease primarily affecting exocrine glands such as the salivary glands, leading to impaired secretion and sicca symptoms. As the mainstay of salivation, salivary gland epithelial cells (SGECs) have an important role in the pathology of pSS. Emerging evidence suggests that the interplay between immunological factors and SGECs may not be the initial trigger or the sole mechanism responsible for xerostomia in pSS, challenging conventional perceptions. To deepen our understanding, current research regarding SGECs in pSS was reviewed. Among the extensive aberrations in cellular architecture and function, this review highlighted certain alterations of SGECs that were identified to occur independently of or in absence of lymphocytic infiltration. In particular, some of these alterations may serve as upstream factors of immuno-inflammatory responses. These findings underscore the significance of introspecting the pathogenesis of pSS and developing interventions targeting SGECs in the early stages of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Tofacitinib, a selective inhibitor of JAK1 and/or JAK3, is considered to alleviate the pulmonary condition of primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD) through its anti-inflammatory and antifibrotic effects. Methods and analysis: This is a single-center, prospective, randomized, open-label trial. The trial will compare a 52-week course of oral tofacitinib with traditional therapy cyclophosphamide (CYC) combined with azathioprine (AZA) in the treatment of pSS-ILD. A total of 120 patients will be randomly assigned into two treatment groups with a 1:1 ratio and followed for 52 weeks from the first dose. The primary endpoint of the study is the increase of forced vital capacity (FVC) at 52 weeks. Secondary endpoints include high-resolution computed tomography (HRCT), diffusion capacity for carbon monoxide of the lung (DLCO), the Mahler dyspnea index, the health-related quality of life (HARQoL) score, the cough symptom score, EULAR Sjögren's syndrome disease activity index (ESSDAI), and safety. Discussion: This study will be the first randomized controlled trial to investigate tofacitinib compared to the traditional regimen of CYC in combination with AZA in the treatment of pSS-ILD, which will provide data on efficacy and safety and further elucidate the role of the JAK-STAT signaling pathway in the development of pSS-ILD. Ethics and dissemination: Before starting the experiment, the research proposal, informed consent (ICF) and relevant documents in accordance with the ethical principles of the Helsinki Declaration and the relevant requirements of the local GCP rules for ethical approval shall be submitted to the ethics committee of the hospital. The ethical approval of this study is reviewed by the Ethics Committee of Tongji Hospital and the ethical approval number is 2021-LCYJ-007. When the experiment is completed, the results will also be disseminated to patients and the public through publishing papers in international medical journals. Trial registration: The study was registered on the Chinese Clinical Trial Registry, www.chictr.org.cn; ID ChiCTR2000031389. [ABSTRACT FROM AUTHOR]

Protein tripartite motif-containing 21 (TRIM21/Ro52), an E3 ubiquitin ligase, is an essential regulator of innate immunity, and its dysregulation is closely associated with the development of autoimmune diseases, predominantly systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). TRIM21 /Ro52 also features anti-cancer and carcinogenic functions according to different malignancies. The interconnected role of TRIM21/Ro52 in regulating autoimmunity and cell metabolism in autoimmune diseases and malignancies is implicated. In this review, we summarize current findings on how TRIM21/Ro52 affects inflammation and tumorigenesis, and investigate the relationship between TRIM21/Ro52 expression and the formation of lymphoma and breast cancer in SLE and pSS populations. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the association between serum bilirubin levels and interstitial lung disease (ILD) in patients with Primary Sjögren's syndrome (pSS). Materials and methods: The retrospectively analysis included 89 consecutive patients with pSS, we collected the clinical materials of pSS patients from the electronic medical records, and all pSS patients were divide into pSS with ILD group and pSS without ILD group. Results: Serum bilirubin levels were significantly lower in pSS patients with ILD than those without ILD (p = 0.010). Serum bilirubin levels showed a significant negative correlation with erythrocyte sedimentation rate (ESR) (r = -0.321, p = 0.002) in patients with pSS. A multivariable logistic regression analysis confirmed that serum bilirubin presented an independent association with ILD in patients with pSS (OR = 0.841, 95%CI:0.728–0.972, p = 0.019). Conclusion: Serum bilirubin is independently associated with ILD and therefore may be a promising marker of ILD in patients with pSS. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is a common chronic systemic autoimmune disorder which primarily affects the exocrine glands. Patients may have extraglandular disease involving multiple organs, including the kidneys. This study aimed at investigating the clinical data and laboratory markers which were associated with renal function damage or renal involvement. Method: One thousand two hundred eighty-eight adult pSS patients from the Department of Rheumatology and Clinical Immunology were enrolled in this retrospective cohort study. And there were 334 patients of them followed up for more than two years for analyzing demographic, clinical data and laboratory markers. Statistical analysis was performed by R software (Version 3.6.2). Result: Nearly 95% of 1288 pSS patients were women, and the positive rates of anti-SSA (Sjögren's syndrome A) and anti-SSB were 63% and 27% respectively. 12% of the pSS patients presented renal involvement with eGFR < 60 mL/min/1.73 m2, and the mean age of hospital presentation, serum creatinine and urea were the highest (P < 0.001), and ANA (antinuclear antibody)-positive, anti-SSB-positive and anti-scl-70-positive were more prevalent in this group. Multivariate analyses showed that age, urea, chlorine and anti-SSA indicate a significant association with renal dysfunction. Potassium, sodium and Jo-1 were also confirmed to be related with decreased renal function. The receiver operating characteristic (ROC) analysis including the above factors showed a good performance on the evaluation of renal injury including eGFR < 60 mL/min/1.73 m2 and eGFR 60 -90 mL/min/1.73 m2 in pSS, with area under curve (AUC) values of 0.957 and 0.821, and high sensitivity (71.1% and 84.4%) and specificity (95.5% and 70.5%). After a more than two years follow-up of anti-SSA positive patients, 34.14% of them developed decreased renal function, and 13.58% of them experienced a progression of renal injury with a 23.64% decrease in eGFR. Conclusion: Age, urea, chlorine, and anti-SSA were highly associated with renal injury in pSS. Early screening for autoantibodies would be meaningful for evaluation and prevention of renal injury in pSS. [ABSTRACT FROM AUTHOR]

Background: Constrictive pericarditis represents a chronic condition and systemic inflammatory diseases are a known, yet uncommon, cause. Pericardial involvement is seldom reported in primary Sjögren's syndrome, usually occurring in association with pericardial effusion or pericarditis. We report a case of constrictive pericarditis with an insidious course and unusual evolution associated with primary Sjögren's syndrome. Due to the challenging nature of the diagnosis, clinical suspicion and multimodality imaging are essential for early identification and prompt initiation of treatment. Long-term outcomes remain uncertain. To the best of our knowledge, no other cases linking this autoimmune disease to constrictive pericarditis have been reported. Case presentation: We present the case of a 48-year-old male patient with moderate alcohol habits and a history of two prior hospitalizations. On the first, the patient was diagnosed with primary Sjögren's syndrome after presenting with pleural effusion and ascites, and empirical corticosteroid regiment was initiated. On the second, two-years later, he was readmitted with complaints of dyspnea and abdominal distension. Thoracic computed tomography revealed a localized pericardial thickening and a thin pericardial effusion, both of which were attributed to his rheumatic disease. A liver biopsy showed hepatic peliosis, which was considered to be a consequence of glucocorticoid therapy. Diuretic therapy was adjusted to symptom-relief, and a tapering corticosteroid regimen was adopted. Four years after the initial diagnosis, the patient was admitted again with recurrent dyspnea, orthopnea and ascites. At this time, constrictive pericarditis was diagnosed and a partial pericardiectomy was performed. Although not completely asymptomatic, the patient reported clinical improvement since the surgery, but still with a need for baseline diuretic therapy. Conclusion: Albeit uncommon, connective tissue disorders, such as primary Sjögren's syndrome, should be considered as a potential cause of constrictive pericarditis, especially in young patients with no other classical risk factors for constriction. In this case, after excluding possible infectious, neoplastic and autoimmune conditions, a primary Sjögren´s syndrome in association with constrictive pericarditis was assumed. This case presents an interesting and challenging clinical scenario, highlighting the importance of clinical awareness and the use of multimodal cardiac imaging for early recognition and treatment. [ABSTRACT FROM AUTHOR]

Background: Primary Sjogren's Syndrome (pSS) is a lymphoproliferative disease with autoimmune characteristics, which is characterized by lymphocyte infiltration of exocrine glands and involvement and dysfunction of extraglandular organs. Renal tubular acidosis (RTA) is a common renal involvement in pSS. This study investigated the phenotypic characteristics of peripheral blood lymphocyte subsets and cytokines in pSS patients complicated with RTA (pSS-RTA). Method: This retrospective study included 25 pSS patients complicated with RTA and 54 pSS patients without RTA (pSS-no-RTA). To examine the level of peripheral lymphocytes subsets, flow cytometry analysis was used. The level of serum cytokines were detected by flow cytometry bead array(CBA). The influencing factors related to the occurrence of pSS-RTA were identified through logistic regression analyze. Results: The absolute number of CD4 + T cells and Th2 cells in peripheral blood were decreased in pSS-RTA patients than pSS-no-RTA patients. Moreover, the absolute number of NK cells and Treg cells were also decreased in pSS-RTA patients than pSS-no-RTA. The level of serum IL-2 was higher in pSS-RTA patients than pSS-no-RTA patients, and is negatively correlated with the number of NK cells, the number and percentage of Th17 cells, and Th17/Treg. Serum IL-2 level is also correlated with various cytokines. Multivariate logistic analysis proved that elevated ESR and ALP were risk factors for pSS complicated with RTA, while Treg was a protective factor. Conclusion: The increase of serum IL-2 level and the decrease of peripheral blood NK cells and Treg cells may be the immune mechanism of the development of pSS-RTA disease. [ABSTRACT FROM AUTHOR]

Background: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease involving multiple organ systems. The Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway is a key pathway involving the pathogenesis of pSS. Baricitinib, a selective JAK1 and JAK2 inhibitor, has been approved for treatment of active rheumatoid arthritis and reported in treatment of some other autoimmune diseases including systemic lupus erythematosus. We have found that baricitinib might be effective and safe in pSS in a pilot study. However, there is no published clinical evidence of baricitinib in pSS. Hence, we conducted this randomized study to further explore the efficacy and safety of baricitinib in pSS. Methods: This is a multi-center, prospective, open-label, randomized study to compare the efficacy of baricitinib + hydroxychloroquine (HCQ) with HCQ alone in pSS patients. We plan to involve 87 active pSS patients with European League Against Rheumatism pSS disease activity index (ESSDAI) ≥ 5 from eight different tertiary centers in China. Patients will be randomized (2:1) to receive baricitinib 4 mg per day + HCQ 400 mg per day or HCQ 400 mg per day alone. We will switch HCQ to baricitinib + HCQ if the patient in the latter group has no ESSDAI response at week 12. The final evaluation will be at week 24. The primary endpoint is the percentage of ESSDAI response, or minimal clinically important improvement (MCII), which was defined as an improvement of ESSDAI at least three points at week 12. The secondary endpoints include EULAR pSS patient-reported index (ESSPRI) response, change of Physician's Global Assessment (PGA) score, serological activity parameters, salivary gland function test, and focus score on labial salivary gland biopsy. Discussion: This is the first randomized controlled study to evaluate the clinical efficacy and safety of baricitinib in pSS. We hope that the result of this study can provide more reliable evidence of the efficacy and safety of baricitinib in pSS. Trial registration: ClinicalTrials.gov NCT05016297. Registered on 19 Aug 2021. [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical features and efficacy of immunosuppressive therapy in patients with primary Sjögren's syndrome (PSS) combined with peripheral neuropathy (PN) syndrome and to explore the risk factors for PN in patients with PSS. Methods: Sixty consecutive patients with PSS admitted to the Department of Rheumatology and Immunology, Wuhan No. 1 Hospital, from January 2014 to June 2020 were analysed retrospectively. Patients were divided into a PN group (N = 15) and a non-PN group (N = 45). The clinical characteristics of the two groups were compared, and the independent risk factors for PN combined with PSS were analysed by multivariate logistic regression. The patients with PSS combined with PN were followed up to observe the effect of immunosuppressive therapy. Results: The patients with PN had a longer course of disease than those without PN (z = − 3.225, P = 0.001), and the incidence of Raynaud's phenomenon, anti-SSB antibody, rheumatoid factor and hyperglobulinaemia was higher (all P < 0.05) in patients with PN than in those without PN. Multivariate logistic regression analysis showed that hyperglobulinaemia, RF and anti-SSB antibodies were independent risk factors for PN with PSS (P < 0.05). Fourteen patients with PSS-PN were treated with immunosuppressants. The clinical symptoms of 10 patients were relieved, and mRS scores of 10 patients were decreased. Conclusion: PN is a common complication in PSS patients. Patients with PSS combined with PN have a longer course of disease and a significantly higher percentage of Raynaud's phenomenon, positive anti-SSB antibody, positive RF and hyperglobulinaemia. Immunosuppressive therapy was effective for partial remission of PN with PSS. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the clinical features and outcomes of childhood-onset primary Sjögren's syndrome (pSS). Methods: Patients less than 18 years old who were diagnosed with pSS by paediatric rheumatologists were included, and all patients were applied the 2002 American-European Consensus Group (ACEG) criteria, the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for pSS, or the 1999 proposed juvenile pSS criteria. The electronic medical records of patients with pSS from 2013 to 2020 were collected and analysed. Results: Thirty-nine patients were included. Of them, 27 (69.2%), 38 (97.4%) and 35 (89.7%) patients fulfilled the AECG criteria, ACR/EULAR criteria and proposed juvenile pSS criteria, respectively. The female:male ratio was 3.9:1. The median ages at first signs or symptoms and at diagnosis were 9.2 (4.7, 14.5) years and 10.9 (6.3, 15.0) years, respectively. The main clinical manifestations were rash or purpura (20, 51.3%), followed by fever (12, 30.8%), glandular enlargement/recurrent parotitis (10, 25.6%), and dry mouth and/or dry eyes (9, 23.1%). Twenty-eight (56.4%) patients had systemic damage, the most common of which was haematological involvement (14, 35.9%), followed by hepatic (13, 33.3%) and renal involvement (8, 20.5%). Thirty-eight (97.4%) patients underwent labial minor salivary gland biopsy, and all exhibited focal lymphocytic sialadenitis. All patients had a global ESSDAI score ≥ 1 at diagnosis, and the median total score at diagnosis was 8 (2, 31). Thirty-six (92.3%) patients were followed up for a median time of 23.6 (7.9, 79.5) months, and three patients developed systemic lupus erythematosus (SLE) at follow-up times of 13.3, 38.8 and 63.8 months. Conclusions: The presentation of childhood-onset pSS is atypical, and extraglandular manifestations and systemic involvement are more common than in adult-onset pSS. Labial salivary gland biopsy is vital for patients with probable pSS. Some patients may develop SLE over time. [ABSTRACT FROM AUTHOR]

Objective: To identify primary Sjögren’s syndrome (pSS) patients with arthralgia at risk for osteoarthritis (OA) or arthritis. Methods: This study included 368 pSS patients admitted to a mono-centric from March 2010 to December 2020. Patients were divided into groups according to whether complicated with OA or arthritis. Data were analyzed to determine the differences in demographical characteristics, symptoms, and laboratory examination. Results: The involvement of the OA joints was predominately knee and spine sites (including cervical and lumbar spine degeneration). When diagnosing arthritis, it was mainly peripheral symmetric polyarthritis, the most affected sites were the interphalangeal and metacarpophalangeal joints. There were significant differences in age, disease duration, uric acid (UA), and total cholesterol (TC) between pSS-OA and pSS-nOA patients (P < 0.050). Logistic regression analysis showed that age (OR = 1.965; P = 0.009) and joint pain (OR = 3.382; P < 0.001) were dangerous factors associated with OA. Interestingly, although the level of UA, TC, and triglycerides (TG) was shown to be positive with OA, there was no statistical significance after the OR was computed in the four-cell table. In pSS-arthritis, EULAR Sjögren's syndrome disease activity index (ESSDAI) (P = 0.011), the frequency of joint pain (P < 0.001), and muscular involvement (P = 0.037) were higher than non-arthritis group. In pSS patients only presenting with joint pain, arthritis patients had higher ESSDAI and system involvements, but lower UA and TG levels compared with OA group (P < 0.050). Conclusion: In pSS patients with arthralgia, OA accounted for the majority. pSS patients with advanced age and more pronounced metabolic characteristics, such as elevated blood lipids and uric acid, was a key factor in groups at risk for OA. However, arthritis patients had higher rates of dry mouth and eye, higher disease activity, antibodies positive, and more organs damage. In the future, it may be necessary to be more cautious in the diagnosis of joint manifestations in pSS patients in order to make the appropriate treatments. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's Syndrome (pSS) is a rare autoimmune disease that is difficult to diagnose due to a variety of clinical presentations, resulting in misdiagnosis and late referral to specialists. To improve early-stage disease recognition, this study aimed to develop an algorithm to identify possible pSS patients in primary care. We built a machine learning algorithm which was based on combined healthcare data as a first step towards a clinical decision support system. Method: Routine healthcare data, consisting of primary care electronic health records (EHRs) data and hospital claims data (HCD), were linked on patient level and consisted of 1411 pSS and 929,179 non-pSS patients. Logistic regression (LR) and random forest (RF) models were used to classify patients using age, gender, diseases and symptoms, prescriptions and GP visits. Results: The LR and RF models had an AUC of 0.82 and 0.84, respectively. Many actual pSS patients were found (sensitivity LR = 72.3%, RF = 70.1%), specificity was 74.0% (LR) and 77.9% (RF) and the negative predictive value was 99.9% for both models. However, most patients classified as pSS patients did not have a diagnosis of pSS in secondary care (positive predictive value LR = 0.4%, RF = 0.5%). Conclusion: This is the first study to use machine learning to classify patients with pSS in primary care using GP EHR data. Our algorithm has the potential to support the early recognition of pSS in primary care and should be validated and optimized in clinical practice. To further enhance the algorithm in detecting pSS in primary care, we suggest it is improved by working with experienced clinicians. [ABSTRACT FROM AUTHOR]

Background: Sjogren's syndrome (SS) is a rare chronic autoimmune disease involving exocrine glands presenting with sicca syndrome, recurrent parotitis and other extraglandular stigmata. SS is well characterized in the adult population with classification criteria; however, primary SS presenting in childhood is poorly defined and rare in males. Recurrent parotitis is the most common presenting symptom in children with primary SS; however, clinical phenotype in children appears more variable than in adults. The lungs are a common extraglandular location for manifestations of primary SS. However, interstitial lung disease (ILD) is rare in children with primary SS. There are only four published reports of ILD associated with primary SS in female children. Here, we present a very rare case of primary SS in a pediatric male with pulmonary manifestations and review of the literature on ILD in childhood-onset primary SS. Case presentation: A 14-year-old White male with a history of chronic severe asthma, recurrent parotitis and idiopathic intracranial hypertension was referred to pediatric rheumatology for evaluation of a positive ANA. In early childhood, he was diagnosed with persistent asthma recalcitrant to therapy. At age 8, he developed recurrent episodes of bilateral parotitis despite multiple treatments with sialoendoscopy. At age 14, respiratory symptoms significantly worsened prompting reevaluation. Lab workup was notable for positive ANA and Sjogren's Syndrome A and B antibodies. Pulmonary function tests showed only a mild obstructive process. Computed tomography of chest was significant for small airway disease, and lung biopsy was positive for mild interstitial lymphocytic inflammation presenting a conflicting picture for ILD. The constellation of findings led to the diagnosis of primary SS with associated pulmonary manifestations. He was treated with hydroxychloroquine, mycophenolate mofetil and oral corticosteroids with resolution of symptoms. Conclusions: Primary SS is a rare disease in the pediatric population that is poorly characterized. This case is the very rare presentation of childhood-onset primary SS with pulmonary manifestations in a male patient. ILD associated with primary SS is also very rare with only four pediatric patients reported in the literature. Collaborative effort is needed to develop pediatric specific diagnostic and treatment guidelines in this rare condition. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is an autoimmune inflammatory disease characterized by dryness of the eyes, mouth and other mucous membranes. Patients with pSS can also present with extraglandular manifestations, such as pulmonary, kidney and nervous system involvement. Central nervous system (CNS) manifestations have rarely been described in pSS.Case Presentation: A 33-year-old man was admitted with a one-month history of dizziness, speech disturbance, and walking instability. His brain enhanced magnetic resonance imaging (MRI) showed symmetrical, enhanced "salt-and-pepper-like" speckled lesions in the brainstem, basal ganglia, and subcortical regions, and his diagnosis was considered possible chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Further examination revealed that anti-SSA antibody was positive, and the Schirmer test and labial salivary gland histopathology were abnormal, which supported the diagnosis of pSS.Conclusion: pSS is a chronic systemic autoimmune disease that involves neurological complications. This case suggests that CNS lesions of pSS can present with clinical and MRI findings similar to those of CLIPPERS. [ABSTRACT FROM AUTHOR]

Background: Sjogren's syndrome, an autoimmune disease of the exocrine glands, results in keratoconjunctivitis sicca, xerostomia, and dental caries. It is often overlooked, considered by clinicians to be a benign disease. However, it can cause life-threatening extra-glandular complications that affect multiple organ systems.Case Presentation: Here we present a 78-year-old Caucasian woman with a history of primary Sjogren's syndrome (pSS) whose symptoms of keratoconjunctivitis sicca were managed managed conservatively. She was evaluated for sub-acute shortness of breath. Imaging showed severe bronchiectasis with features of lymphocytic interstitial pneumonia. She also had exudative bilateral pleural effusions and skin ulcers, likely vasculitic in origin. The workup was significant for anti-Ro antibody, pancytopenia, hypocomplementia, cryoglobulinemia and monoclonal gammopathy, all of which reflect disease severity. Although there was no evidence of malignancy, she developed B-cell non-Hodgkin lymphoma during follow-up.Conclusions: Primary Sjogren's syndrome can result in severe multi-organ disease. Pleural effusions are a rare complication of pSS, with only ten cases reported in the literature over the last 30 years, and tend to respond well to steroids. Prognostic biomarkers for disease severity include hypocomplementia, cryoglobulinemia, monoclonal gammopathy, and hypergammaglobulinemia. In this report we review the literature and the management of the disease. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation of T and B lymphocytes, and infiltration of tissue lymphocytes. With the development of modern medicine, although research on the pathogenesis, diagnosis, and treatment of pSS has made significant progress, its pathogenesis has not been fully understood. Meanwhile, in the era of individualized treatment, it remains essential to further explore early diagnosis and treatment methods. Exosomes, small vesicles containing proteins and nucleic acids, are a subtype of extracellular vesicles secreted by various cells and present in various body fluids. Exosomes contribute to a variety of biological functions, including intercellular signal transduction and pathophysiological processes, and may play a role in immune tolerance. Therefore, exosomes are key to understanding the pathogenesis of diseases. Exosomes can also be used as a therapeutic tool for pSS because of their biodegradability, low immunogenicity and toxicity, and the ability to bypass the blood–brain barrier, implying the prospect of a broad application in the context of pSS. Here, we systematically review the isolation, identification, tracing, and mode of action of extracellular vesicles, especially exosomes, as well as the research progress in the pathogenesis, diagnosis, and treatment of pSS. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is an auto-immune disease characterized by sialadenitis and dacryoadenitis with lymphoplasmacytic cell infiltration. In pSS, not only sicca symptoms, but also extra-glandular involvement induced by immune abnormalities based on pSS occurs. Renal involvement is one such important life-threatening extra-glandular involvement. Although the aberrant glycosylated IgA in pSS as a product of over-activated B cells is a risk factor of renal involvement, its association has not been clarified. Here we report a case of glomerulonephritis (GN) induced by immune complexes (IC) composed of galactose-deficient IgA1 (Gd-IgA1) in a patient with pSS.Case Presentation: A 48-year-old Japanese woman with pSS was admitted to our hospital because of a two-month history of nephrotic syndrome. Seven years before she had been diagnosed with pSS from keratoconjunctivitis sicca, elevation of serum anti-Ro/SSA antibody titer and lymphoplasmacytic cell infiltration around salivary ducts of the small salivary glands. Renal biopsy revealed diffuse bubbling appearance in glomerular basement membrane (GBM) with scarce mesangial proliferation. Immunofluorescence showed granular IgA, C3 and Gd-IgA1 staining of GBM. Light chain staining showed no monoclonality. Electron microscopy showed electron dense deposits mainly in the intra-membranous and paramesangial areas and slightly in the subepithelial area. Additional serum analysis confirmed elevation of Gd-IgA1 (13.5 μg/mL), which was comparable with that seen in IgA nephropathy, and qualitative enzyme-linked immunosorbent assay of IgA-containing circulating immune complex (IgA-CIC) was positive. Thus, we diagnosed GN induced by IC composed of Gd-IgA1. Furthermore, retrospectively performed immunofluorescence of the small salivary gland evaluated at the diagnosis of pSS showed positive Gd-IgA1 staining of infiltrating lymphoplasmacytic cells. Therefore, we concluded that Gd-IgA1 produced by over-activated B cells in pSS formed circulating IC and thereby induced GN. After induction therapy with high dose prednisolone and mycophenolate mofetil, the nephrotic syndrome remitted within 3 weeks, the serum Gd-IgA1 level decreased to the normal range (3.8 μg/mL), and serum IgA-CIC disappeared in the 6th month after induction therapy.Conclusions: Our findings clearly demonstrate an association between aberrant glycosylated IgA and the renal involvement seen in pSS, thereby helping to clarify the renal significance of aberrant glycosylated IgA in pSS. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effects of systemic parameters, laboratory findings, oral parameters, and other ocular surface parameters on ocular surface epithelial damage in patients with primary Sjögren's syndrome (pSS).Methods: A total of 82 dry eye disease (DED) patients with pSS were enrolled in this study. Ocular surface epithelial damage was measured by ocular staining score (OSS). Systemic parameters, laboratory findings including serologic markers, oral parameters, and other ocular surface parameters were collected. Other ocular surface parameter assessments such as the Schirmer's test, fluorescein tear breakup time, meibomian gland examinations, noninvasive keratographic tear film break-up time measurements using the Keratograph® 5 M were performed, and the Ocular Surface Disease Index was determined.Results: In a multivariate analysis, decreased age and increased duration of pSS were significantly related to increased logarithm-transformed OSS (β = -0.011, P = 0.043 and β = 0.003, P = 0.008). Among the ocular surface parameters, decreased fluorescein tear breakup time and increased MGD grade were significantly associated with increased logarithm-transformed OSS (β = -0.183, P < 0.001 and β = 0.192, P = 0.049).Conclusions: Ocular surface epithelial damage in patients with pSS was associated with young age, long duration of disease, unstable tear film, and decreased meibomian gland function. [ABSTRACT FROM AUTHOR]

Exosomes are cell-derived membranous vesicles of endosomal origin secreted by all type of cells and present in various body fluids. Exosomes are enriched in peptides, lipids, and nucleic acids, emerging as vital modulators in intercellular communication. Exosomes are increasingly being evaluated as biomarkers for diagnosis and prognosis of diseases, because the constituents of exosomes could be reprogrammed depending on the states of diseases. These features also make exosomes a research hotspot in oral diseases in recent years. In this review, we outlined the characteristics of exosomes, focused on the differential expressions and altered biological functions of exosomes in oral diseases, including oral squamous cell carcinoma, oral leukoplakia, periodontitis, primary Sjögren's syndrome, oral lichen planus, as well as hand foot and mouth disease. Besides, accumulated evidence documents that it is implementable to consider the natural nanostructured exosomes as a new strategy for disease treatment. Herein, we highlighted the therapeutic potential of exosomes in oral tissue regeneration, oncotherapy, wound healing, and their superiority as therapeutic drug delivery vehicles. [ABSTRACT FROM AUTHOR]

Background: CD72, a co-receptor of B cell receptor (BCR), has been reported to have both positive and negative effects on B cell functions in several immunological diseases. The B cell plays an important role in the pathogenesis of primary Sjogren's syndrome (pSS). However, whether CD72 is involved in the process remains unknown. This study aimed to observe the possible role of CD72 in the pathogenesis of pSS. Results: A total of 60 cases who fulfilled the American-European Consensus Group (AECG) criteria for the diagnosis of pSS and 61 gender and age-matched healthy controls were recruited in this study. The percentage of CD72+ B cells was 85.31 ± 8.37% in pSS patients and 76.91 ± 8.50% in healthy controls(p < 0.001). The percentage of CD72+ B cells was correlated to serum IgG levels in patients [β = 0.018(0.001–0.036), p = 0.034]. The level of serum soluble CD72 was significantly higher in pSS patients than the one in healthy controls (0.41 (0.29) vs 0.07 (0.08) ng/mL, p < 0.001). Conclusions: The percentage of CD72+ B cells was upregulated in pSS patients and was correlated to the serum IgG level, which revealed the hyperactivity of B cells in this disease. The serum soluble CD72 level was also increased in pSS patients. These results indicated a potential role of CD72 in the pathogenesis of pSS. [ABSTRACT FROM AUTHOR]

Background: Regulatory T cells (Tregs) are crucial in maintaining immune tolerance and immune homeostasis, but their role in idiopathic pulmonary fibrosis (IPF) is unclear. This study was designed to explore the role of Tregs in IPF.Methods: Percentages of Tregs and their subpopulations in peripheral blood (PB) and bronchoalveolar lavage (BAL) samples were determined by flow cytometry in 29 patients with IPF, 19 patients with primary Sjögren's syndrome-related interstitial pneumonia (pSS-IP), and 23 healthy controls (HCs).Results: In peripheral blood, no difference was found in CD4+CD25+Foxp3+ Treg percentages among patients with IPF, pSS-IP, or HCs. However, activated Treg (aTreg) fractions among CD4+ T cells increased significantly in IPF compared with pSS-IP or HCs. Being consistent with the result from the PB, aTreg fractions among CD4+ T cells in IPF also increased significantly compared with pSS-IP or HCs, accompanied by increased fraction III compared with HCs in BAL. IPF patients had lower levels of resting Tregs (rTregs) from the thymus than did HCs, whereas aTreg levels originating from the thymus did not significantly differ from HCs. Both rTregs and aTregs proliferated in IPF, with aTregs being more proliferative than rTregs. Both rTregs and aTregs significantly inhibited proliferation of CD4+ T lymphocytes in vitro. The percentage of aTregs was correlated negatively with predicted diffusing capacity values for carbon monoxide and positively with GAP index in IPF.Conclusions: Our study showed the imbalance between subpopulations of Tregs in IPF. Increased aTregs proportion in the peripheral blood correlated inversely with disease severity. [ABSTRACT FROM AUTHOR]

Background: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder defined by xerostomia and keratoconjunctivitis sicca, and its etiology remains unknown. N6-methyladenosine (m 6 A) is the predominant posttranscriptional modification in eukaryotic mRNAs and is dynamically regulated by m 6 A regulators. Dysregulation of m 6 A modification is closely associated with several autoimmune disorders, but the role of m 6 A modification in pSS remains unknown. This study investigated the potential role of m 6 A and m 6 A-related regulators in pSS patients with dry eye., Methods: This cross-sectional study included forty-eight pSS patients with dry eye and forty healthy controls (HCs). Peripheral blood mononuclear cells (PBMCs) were isolated, and the level of m 6 A in total RNA was measured. The expression of m 6 A regulators was determined utilizing real-time PCR and western blotting. The serological indicators detected included autoantibodies, immunoglobulins (Igs), complement factors (Cs), and inflammatory indicators. Dry eye symptoms and signs were measured, including the ocular surface disease index, Schirmer's test (ST), corneal fluorescein staining score (CFS), and tear break-up time. Spearman's correlation coefficient was employed to assess the associations of m 6 A and m 6 A-related regulator expression with clinical characteristics., Results: The expression level of m 6 A was markedly increased in the PBMCs of pSS patients with dry eye compared to HCs (P value <0.001). The relative mRNA and protein expression levels of the m 6 A regulators methyltransferase-like 3 (METTL3) and YT521-B homology domains 1 were markedly elevated in pSS patients with dry eye (both P value <0.01). The m 6 A RNA level was found to be positively related to METTL3 expression in pSS patients (r = 0.793, P value <0.001). Both the m 6 A RNA level and METTL3 mRNA expression correlated with the anti-SSB antibody, IgG, ST, and CFS (all P values < 0.05). The m 6 A RNA level was associated with C4 (r = -0.432, P value = 0.002), while METTL3 mRNA expression was associated with C3 (r = -0.313, P value = 0.030)., Conclusions: Our work revealed that the upregulation of m 6 A and METTL3 was associated with the performance of serological indicators and dry eye signs in pSS patients with dry eye. METTL3 may contribute to the pathogenesis of dry eye related to pSS., (© 2023. The Author(s).)

Background: Labial salivary gland biopsy (LSGB) is the most important diagnostic tool for the diagnosis of Sjögren's syndrome (SS), but its diagnostic value is rarely studied. This study assessed the sensibility and specificity of LSGB, and the clinical profiles of patients who were referred for biopsy. Methods: Retrospective analysis of the histopathological reports from LSGB and medical report data from patients who underwent LSGB between 2008 and 2011 was conducted. Results: About 290 biopsies were performed and 74 were excluded due to insufficient clinical data. Of the 216 patients, 0.46% was carrier of hepatitis C virus, 30.1% had primary SS (pSS), and 8.8% had secondary SS (sSS). Of the samples, 94.3% presented dryness symptoms, 51.6% experienced dryness only, 42.7% had systemic manifestations, and 66.9% presented low unstimulated salivary flow and/or Schirmer's test. LSGB was necessary in 67.6% to confirm the presence of SS based on the American-European Consensus Group 2002 criteria (AECG). Based on specialist's opinion, sensibility level was 86.57%, and specificity was 97.43%. Positive predictive value (PPV) was 95%, and negative predictive value (NPV) was 92.6%. Determined accuracy was 93.3%. Concordance (kappa coefficient) of LSGB and specialist's opinion was 0.851, and LSGB with AECG criteria was 0.806. Of the 98 patients referred with fibromyalgia and dryness, 36.7% had SS and LSBG focus score of = 1. Patients with SS were older, and showed more severe lachrymal and salivary dysfunctions, greater frequency of fibromyalgia, anti-nuclear antibodies (ANA), anti-SSA-Ro, and anti-SSB-La. Conclusions: Labial salivary gland biopsy has high sensibility, specificity, positive and negative predictive values for diagnosis of pSS. In the clinical practice, it is useful, especially for those patients with glandular dysfunctions and negative antibodies. [ABSTRACT FROM AUTHOR]

Background: Sjögren's syndrome is a systemic autoimmune disease in which lymphatic cells destroy the salivary and lacrimal glands. Glomerulonephritis is thought to be a rare occurrence in primary Sjögren's syndrome. Furthermore, concurrent glomerular involvement and lymphoma in patients with Sjögren's syndrome has seldom been reported. Case presentation: A 52-year-old woman with primary Sjögren's syndrome developed membranous glomerulonephritis and Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL). She was diagnosed with Sjögren's syndrome based on the dry eyes, dry mouth, positive anti-nuclear antibody test, anti-Ro (SS-A) antibody, salivary gland biopsy, and salivary scintigraphy. Moreover, renal biopsy confirmed the diagnosis of membranous glomerulonephritis. Three months later, her small bowel was perforated with pneumoperitoneum, and the biopsyrevealed Epstein-Barr virus-positive DLBCL. Conclusions: We observed the first case of primary Sjögren's syndrome associated with Epstein-Barr Virus-positive DLBCL and membranous glomerulonephritis. Because of the possibility of malignancy-associated membranous glomerulonephritis in patients with primary Sjögren's syndrome, we should be careful and examine such patients for hidden malignancy. [ABSTRACT FROM AUTHOR]