Sjögren's syndrome and Parkinson's Disease: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous observational studies have reported an association between Sjögren's syndrome (SS) and an increased risk of Parkinson's Disease (PD). However, the causal relationship between these conditions remains unclear. The objective of this study was to investigate the causal impact of SS on the risk of developing PD, utilizing the Mendelian randomization (MR) approach. METHODS: We conducted a bidirectional MR analysis using publicly available genome-wide association studies (GWAS) data. The primary analysis utilized the inverse-variance weighted (IVW) method. Complementary methods, such as MR-Egger regression, weighted mode, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were utilized to identify and correct for the presence of horizontal pleiotropy. RESULTS: The IVW MR analysis revealed no significant association between SS and PD (IVW: OR = 1.00, 95% CI = 0.94-1.07, P = 0.95). Likewise, the reverse MR analysis did not identify any significant causal relationship between PD and SS (IVW: OR = 0.98, 95% CI = 0.85-1.12, P = 0.73). The results from MR-Egger regression, weighted median, and weighted mode approaches were consistent with the IVW method. Sensitivity analyses suggested that horizontal pleiotropy is unlikely to introduce bias to the causal estimates. CONCLUSION: This study does not provide evidence to support the assertion that SS has a conclusive impact on the risk of PD, which contradicts numerous existing observational reports. Further investigation is necessary to determine the possible mechanisms behind the associations observed in these observational studies.

Primary Sjögren's syndrome independently promotes premature subclinical atherosclerosis.

OBJECTIVES: Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren's syndrome (pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage. METHODS: Patients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers. RESULTS: Data were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6-65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren's Syndrome Disease Activity Index (p<0.001) and anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed. CONCLUSIONS: Subclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.

Oral health status, related behaviours and perceived stress in xerostomia, Sicca and Sjögren's syndromes patients - a cross-sectional study.

BACKGROUND: Mouth dryness increases the risk of some oral health-related conditions. Furthermore, it is unclear if patients with dry mouth engage in appropriate oral health-related behaviours. The study examined oral health, related behaviours, and perceived stress in dry-mouth patients and compared them to matched controls without mouth dryness. METHODS: Information about 182 dry-mouth patients and 302 age- and sex-matched subjects was retrieved. Three dry mouth groups: xerostomia, Sicca syndrome and Sjögren's syndrome, were formed based on patient self-reported and objectively assessed symptoms. The World Health Organization's Oral Health for Adults and Perceived Stress Scale (PSS-10) questionnaires inquired about sociodemographic characteristics, oral health-related behaviours, and self-perceived stress. Clinical oral health assessments included: caries experience measured as total numbers of decayed (DS), missing (MS), filled surfaces (FS), number of remaining teeth, erosive tooth wear and extent of periodontal pocketing. Data were analyzed using bivariate and multivariable tests. RESULTS: The dry-mouth participants had higher mean (SD) DMFS scores than their matched controls: xerostomia patients vs. controls: 74.6 (34.4) and 66.3 (35.4), Sicca syndrome patients vs. controls: 88.3 (34.0) and 70.1 (33.9), and Sjögren's syndrome patients vs. controls: 95.7 (31.5) and 74 (33.2). In comparison to controls, individuals with Sicca and patients with Sjögren's syndromes had lower mean (SD) number of remaining teeth, 15.9 (10.1) vs. 21.7 (8.4) and 13.8 (10.0) vs. 20.1 (9.2), and a lower mean (SD) extent of periodontal pocketing, 20.7 (28.6) vs. 41.1 (31.0), and 21.2 (24.1) vs. 34.8 (34.2), respectively. Xerostomia, Sicca syndrome and Sjögren's syndrome patients had higher odds of using fluoridated toothpaste; OR 1.8 (95%CI 1.1-2.9), OR 5.6 (95%CI 1.7-18.3) and OR 6.9 (95%CI 2.2-21.3), respectively. Participants with Sjögren's syndrome had lower odds of the last dental visit being within the last year; OR 0.2 (95%CI 0.1-0.8). CONCLUSIONS: Dry-mouth patients had higher caries experience and fewer teeth than comparison groups but a lower extent of periodontal pocketing. Even though more participants with dry mouth used fluoridated toothpastes, their oral health-related behaviours were not optimal.

Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sjögren's disease.

Childhood Sjögren's disease represents critically unmet medical needs due to a complete lack of immunological and molecular characterizations. This study presents key immune cell subsets and their interactions in the periphery in childhood Sjögren's disease. Here we show that single-cell RNA sequencing identifies the subsets of IFN gene-enriched monocytes, CD4+ T effector memory, and XCL1+ NK cells as potential key players in childhood Sjögren's disease, and especially in those with recurrent parotitis, which is the chief symptom prompting clinical visits from young children. A unique cluster of monocytes with type I and II IFN-related genes is identified in childhood Sjögren's disease, compared to the age-matched control. In vitro regulatory T cell functional assay demonstrates intact functionality in childhood Sjögren's disease in contrast to reduced suppression in adult Sjögren's disease. Mapping this transcriptomic landscape and interplay of immune cell subsets will expedite the understanding of childhood Sjögren's disease pathogenesis and set the foundation for precision medicine.

Extranodal Rosai-Dorfman disease manifesting as Sjögren's syndrome combined with panuveitis and hypertrophic pachymeningitis: a case report and review of literature.

Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis characterized by massive lymphadenopathy and systemic extranodal lesions. We present the case of a 28-year-old woman who presented with recurrent blurred vision in her right eye for 3 months. She developed blindness and atrophy in her left eye a decade prior to presentation. She subsequently developed headache, fever, and impaired mental status. Cranial magnetic resonance imaging indicated hypertrophic pachymeningitis (HP), and 18F-fluoro-2-deoxy-2-d-glucose (FDG) positron emission tomography/computed tomography revealed significant FDG uptake in the left dura mater. Autoimmune testing revealed elevated anti-nuclear, anti-SS-A, and anti-SS-B antibody levels. Incisional biopsy of the atrophic eyeball revealed RDD with marked polyclonal plasmacytosis. The patient was diagnosed with RDD accompanied by multisystem involvement, including Sjögren's syndrome (SS), panuveitis, and HP. Treatment with methylprednisolone for several weeks resulted in significant improvement. This is the first reported case of RDD presenting with SS in combination with panuveitis and HP. Although RDD is rarely diagnosed in young patients, interdisciplinary collaboration is essential to prevent a delayed diagnosis.

A relatively rare traditional Chinese medicine pattern of primary Sjögren syndrome: A case report.

RATIONALE: This report presents a unique case of a patient diagnosed with Primary Sjögren's syndrome and a relatively rare traditional Chinese medicine pattern, known as the combined cold and heat pattern and cold-dampness syndrome. The patient's condition was successfully managed using Chinese herbal medicine, specifically the modified Da-Chai-Hu decoction and Linggui Zhugan decoction. PATIENT CONCERNS: A 56-year-old woman had chronic dry eye and mouth for over 10 years. She was initially managed with traditional Chinese herbal medicine (TCHM) prescriptions, including the Zengye decoction, but the therapeutic effects were unsatisfactory. As the disease progressed, she was diagnosed with an anxiety disorder due to symptoms of vexation and insomnia. Treatment with alprazolam and venlafaxine failed to alleviate these symptoms. Recently, her general condition gradually worsened, with symptoms including a bitter taste in her mouth, dizziness, hot flashes, chills, poor appetite, chest discomfort, and constipation. DIAGNOSES: After a series of examinations, including a Schirmer test and labial gland biopsy, she was diagnosed with Sjögren's syndrome. INTERVENTIONS: Despite regular treatment with pilocarpine, sodium hyaluronate eye drops, venlafaxine, and alprazolam, the dry mouth symptoms intensified. Consequently, she sought further intervention through the TCHM. OUTCOMES: After 8 weeks of treatment with the modified Da-Chai-Hu decoction and Linggui Zhugan decoction, she reported a significant improvement in her dryness-related symptoms and sleep quality. LESSONS: This case report demonstrates that TCHM can effectively treat Primary Sjögren's syndrome, and should be considered for broader applications. Furthermore, this underscores the importance of tailoring treatment formulas to patients by identifying their specific syndrome differentiation in a clinical setting.

Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sjögren's Syndrome.

Objective As primary Sj?gren's syndrome (pSS) primarily affects the salivary glands, saliva can serve as an indicator of the glands' pathophysiology and the disease's status. This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis.Methods The discovery set contained 49 samples (24 from pSS and 25 from age- and gender-matched healthy controls [HCs]) and the validation set included 25 samples (12 from pSS and 13 from HCs). Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio. Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition (DIA) strategy on a 2D LC?HRMS/MS platform to reveal differential proteins. The crucial proteins were verified using DIA analysis and annotated using gene ontology (GO) and International Pharmaceutical Abstracts (IPA) analysis. A prediction model for SS was established using random forests.Results A total of 1,963 proteins were discovered, and 136 proteins exhibited differential representation in pSS patients. The bioinformatic research indicated that these proteins were primarily linked to immunological functions, metabolism, and inflammation. A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm, and was validated as the predictive biomarkers exhibiting good performance with area under the curve (AUC) of 0.817 for discovery set and 0.882 for validation set.Conclusions The candidate protein panel discovered may aid in pSS diagnosis. Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients. DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Novel and potential future therapeutic options in systemic autoimmune diseases.

Autoimmune inflammation is caused by the loss of tolerance to specific self-antigens and can result in organ-specific or systemic disorders. Systemic autoimmune diseases affect a significant portion of the population with an increasing rate of incidence, which means that is essential to have effective therapies to control these chronic disorders. Unfortunately, several patients with systemic autoimmune diseases do not respond at all or just partially respond to available conventional synthetic disease-modifying antirheumatic drugs and targeted therapies. However, during the past few years, some new medications have been approved and can be used in real-life clinical settings. Meanwhile, several new candidates appeared and can offer promising novel treatment options in the future. Here, we summarize the newly available medications and the most encouraging drug candidates in the treatment of systemic lupus erythematosus, rheumatoid arthritis, Sjögren's disease, systemic sclerosis, systemic vasculitis, and autoimmune myositis.

Unprecedented complexity of six coexisting autoimmune diseases: A case report.

INTRODUCTION: Autoimmune disorders often exhibit interconnectedness, although encountering multiple autoimmune conditions in a single patient is uncommon. Multiple autoimmune syndrome is characterized by the presence of at least three distinct autoimmune diseases in an individual. This report outlines the case of a middle-aged woman diagnosed with autoimmune thyroiditis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, and antisynthetase syndrome. Additionally, it includes a literature review encompassing multiple autoimmune syndromes involving five or more autoimmune diseases. OBSERVATION: A 57-year-old woman, with no previous medical history, presented with fever, extensive muscle weakness, progressive exertional dyspnea, inflammatory polyarthralgia, dysphagia, and dry mouth. Clinical examination revealed muscular deficit in the scapular and pelvic girdles, distal muscular deficit, synovitis in the wrists, and features indicative of "mechanic's hand". Laboratory examinations showed cytolysis, cholestasis, elevated muscle enzymes, hypergammaglobulinemia and elevated thyroid stimulating hormone. Immunoassays showed positive results for antinuclear antibodies, anti-histidyl-t-RNA synthetase, anti-Sjögren's-syndrome-related antigen A, anti-ribonucleic-acid-polymerase-III-RP155, anti-fibrillarin, anti-mitochondrial, anti-liver/kidney microsomal type 1, anti-glycoprotein 210, and anti-thyroid peroxidase antibodies. Further investigations led to the diagnosis of a multiple autoimmune syndrome involving autoimmune thyroiditis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, and antisynthetase syndrome. The patient received treatment with intravenous immunoglobulins, corticosteroids, azathioprine, and ursodeoxycholic acid, which resulted in favorable clinical and biological outcomes. CONCLUSION: This patient presented with six concurrent distinct autoimmune disorders, categorizing this case as a type two multiple autoimmune syndrome. The identification of antisynthetase syndrome notably distinguishes this case.

[Clinicopathological features of Sjogren's syndrome complicated with liver injury].

Objective: To study the clinicopathological features of Sjogren's syndrome (SS) with liver injury and to improve the understanding of this disease. Methods: Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson's trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted. Results: The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group (P=0.006) and NALFD group (P=0.011) were significantly higher than those in other groups (P<0.05). Conclusions: The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

The Florida Scoring System for stratifying children with suspected Sjögren's disease: a cross-sectional machine learning study.

BACKGROUND: Childhood Sjögren's disease is a rare, underdiagnosed, and poorly-understood condition. By integrating machine learning models on a paediatric cohort in the USA, we aimed to develop a novel system (the Florida Scoring System) for stratifying symptomatic paediatric patients with suspected Sjögren's disease. METHODS: This cross-sectional study was done in symptomatic patients who visited the Department of Pediatric Rheumatology at the University of Florida, FL, USA. Eligible patients were younger than 18 years or had symptom onset before 18 years of age. Patients with confirmed diagnosis of another autoimmune condition or infection with a clear aetiological microorganism were excluded. Eligible patients underwent comprehensive examinations to rule out or diagnose childhood Sjögren's disease. We used latent class analysis with clinical and laboratory variables to detect heterogeneous patient classes. Machine learning models, including random forest, gradient-boosted decision tree, partial least square discriminatory analysis, least absolute shrinkage and selection operator-penalised ordinal regression, artificial neural network, and super learner were used to predict patient classes and rank the importance of variables. Causal graph learning selected key features to build the final Florida Scoring System. The predictors for all models were the clinical and laboratory variables and the outcome was the definition of patient classes. FINDINGS: Between Jan 16, 2018, and April 28, 2022, we screened 448 patients for inclusion. After excluding 205 patients due to symptom onset later than 18 years of age, we recruited 243 patients into our cohort. 26 patients were excluded because of confirmed diagnosis of a disorder other than Sjögren's disease, and 217 patients were included in the final analysis. Median age at diagnosis was 15 years (IQR 11-17). 155 (72%) of 216 patients were female and 61 (28%) were male, 167 (79%) of 212 were White, and 20 (9%) of 213 were Hispanic, Latino, or Spanish. The latent class analysis identified three distinct patient classes: class I (dryness dominant with positive tests, n=27), class II (high symptoms with negative tests, n=98), and class III (low symptoms with negative tests, n=92). Machine learning models accurately predicted patient class and ranked variable importance consistently. The causal graphical model discovered key features for constructing the Florida Scoring System. INTERPRETATION: The Florida Scoring System is a paediatrician-friendly tool that can be used to assist classification and long-term monitoring of suspected childhood Sjögren's disease. The resulting stratification has important implications for clinical management, trial design, and pathobiological research. We found a highly symptomatic patient group with negative serology and diagnostic profiles, which warrants clinical attention. We further revealed that salivary gland ultrasonography can be a non-invasive alternative to minor salivary gland biopsy in children. The Florida Scoring System requires validation in larger prospective paediatric cohorts. FUNDING: National Institute of Dental and Craniofacial Research, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Heart, Lung, and Blood Institute, and Sjögren's Foundation.

A Smartphone App to Support Self-Management for People Living With Sjögren's Syndrome: Qualitative Co-Design Workshops.

BACKGROUND: Sjögren's syndrome (SS) is the second most common autoimmune rheumatic disease, and the range of symptoms includes fatigue, dryness, sleep disturbances, and pain. Smartphone apps may help deliver a variety of cognitive and behavioral techniques to support self-management in SS. However, app-based interventions must be carefully designed to promote engagement and motivate behavior change. OBJECTIVE: We aimed to explore self-management approaches and challenges experienced by people living with SS and produce a corresponding set of design recommendations that inform the design of an engaging, motivating, and evidence-based self-management app for those living with SS. METHODS: We conducted a series of 8 co-design workshops and an additional 3 interviews with participants who were unable to attend a workshop. These were audio recorded, transcribed, and initially thematically analyzed using an inductive approach. Then, the themes were mapped to the Self-Determination Theory domains of competency, autonomy, and relatedness. RESULTS: Participants experienced a considerable demand in the daily work required in self-managing their SS. The condition demanded unrelenting, fluctuating, and unpredictable mental, physical, and social efforts. Participants used a wide variety of techniques to self-manage their symptoms; however, their sense of competency was undermined by the complexity and interconnected nature of their symptoms and affected by interactions with others. The daily contexts in which this labor was occurring revealed ample opportunities to use digital health aids. The lived experience of participants showed that the constructs of competency, autonomy, and relatedness existed in a complex equilibrium with each other. Sometimes, they were disrupted by tensions, whereas on other occasions, they worked together harmoniously. CONCLUSIONS: An SS self-management app needs to recognize the complexity and overlap of symptoms and the complexities of managing the condition in daily life. Identifying techniques that target several symptoms simultaneously may prevent users from becoming overwhelmed. Including techniques that support assertiveness and communication with others about the condition, its symptoms, and users' limitations may support users in their interactions with others and improve engagement in symptom management strategies. For digital health aids (such as self-management apps) to provide meaningful support, they should be designed according to human needs such as competence, autonomy, and relatedness. However, the complexities among the 3 Self-Determination Theory constructs should be carefully considered, as they present both design difficulties and opportunities.

Ocular manifestations of liver disease: an important diagnostic aid.

PURPOSE: This review examined existing literature to determine various ocular manifestations of liver pathologies, with a focus on metabolic deficiencies as well as viral and immune liver conditions. METHODS: Recent data were compiled from PubMed from 2000 to 2020 using keywords that were relevant to the assessed pathologies. Ocular presentations of several liver pathologies were researched and then summarized in a comprehensive form. RESULTS: Several ocular manifestations of liver disease were related to vitamin A deficiency, as liver disease is associated with impaired vitamin A homeostasis. Alcoholic liver cirrhosis can result in vitamin A deficiency, presenting with Bitot spots, xerosis, and corneal necrosis. Congenital liver diseases such as mucopolysaccharidoses and peroxisomal disorders are also linked with ocular signs. Viral causes of liver disease have associations with conditions like retinal vasculitis, keratoconjunctivitis sicca, retinopathies, Mooren's ulcer, and Sjogren's syndrome. Autoimmune hepatitis has been linked to peripheral ulcerative keratitis and uveitis. CONCLUSIONS: Building strong associations between ocular and liver pathology will allow for early detection of such conditions, leading to the early implementation of management strategies. While this review outlines several of the existing connections between hepatic and ophthalmic disease, further research is needed in the area in order to strengthen these associations.

Development of a nomogram for membranous nephropathy prediction in patients with primary Sjögren's syndrome: a 6-year retrospective study.

Objectives: Nephritis is a life-threatening complication of primary Sjögren's syndrome (pSS), with membranous nephropathy (MN) being prevalent. Renal biopsy is the gold standard for MN diagnosis, but it is invasive and cannot be repeatedly performed. This study aimed to develop a nomogram for the prediction of MN in patients with pSS. Methods: This retrospective study included patients with pSS admitted to the Rheumatology and Immunology Department of the First Affiliated Hospital of China Medical University between January 2015 and January 2021. A nomogram was developed using multivariable logistic regression analysis and evaluated using receiver operating characteristic (ROC) curve analysis. Bootstrap resampling analysis (1,000 times) was performed to evaluate the nomogram for discrimination and the calibration curve for consistency. Results: A total of 237 patients with pSS [aged 53.00 (44.00, 61.00) years] were included, with 35 pSS-MN patients. Based on clinical practice and multivariable logistic regression analysis, seven variables associated with pSS-MN were selected, including white blood cells, creatine, complement 3, rheumatoid factor, antinuclear antibodies, anti-SSA antibody, and interstitial lung disease. The area under the ROC curve was 0.860 (95% confidence interval: 0.796-0.919), indicating good predictive power. In addition, the nomogram exhibited excellent performance, as demonstrated by the calibration curve and decision curve analysis. Conclusion: This study developed a risk prediction nomogram for MN in patients with pSS, with high predictive power. It may be used to improve the management of patients with pSS.

Sjögren: unique surname, two men, four syndromes and one disease.

Henrik and Torsten Sjögren (/'ʃoʊɡrən/ or SHOH-grən) were two Swedish physicians living in the same period, but completely unrelated, except for their notable contributions to Medicine. The first one described keratoconjunctivitis sicca, afterward called Sjögren's syndrome, and a fishing net aspect retinal pigmentation affecting visual acuity, nowadays known as Sjögren reticular dystrophy. The last one contributed to the understanding of Spielmeyer-Sjögren disease, Marinesco-Sjögren, and Sjögren-Larsson syndromes, all related to genetic disorders and neurological symptoms. In this paper, we aim to describe each disorder, in order to avoid any misunderstanding in diagnosis and for historical record.

Henrik e Torsten Sjögren (/ˈʃoʊɡrən/ ou SHOH-grən) foram dois médicos suecos que viveram na mesma época, mas não tinham nenhuma relação entre si, exceto por suas notáveis contribuições à medicina. O primeiro descreveu a ceratoconjuntivite sicca, posteriormente chamada de síndrome de Sjögren, e uma pigmentação da retina com aspecto de rede de pesca que afeta a acuidade visual, hoje conhecida como distrofia reticular de Sjögren. O último contribuiu para a compreensão da doença de Spielmeyer-Sjögren, das síndromes de Marinesco-Sjögren e Sjögren-Larsson, todas relacionadas a distúrbios genéticos e sintomas neurológicos. Neste artigo, pretendemos descrever cada desordem, a fim de evitar qualquer mal-entendido no diagnóstico e para registro histórico.

Distinctive profile of monomeric and polymeric anti-SSA/Ro52 immunoglobulin A1 isoforms in saliva of patients with primary Sjögren's syndrome and Sicca.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva. METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls. RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

Non-invasive imaging for predicting labial salivary gland biopsy outcomes in patients with suspected primary Sjögren syndrome.

To identify the value of salivary gland ultrasound (SGUS) combined with magnetic resonance imaging (MRI) and magnetic resonance sialography (MRS) in predicting the results of labial salivary gland biopsy (LSGB) in patients with suspected primary Sjögren syndrome (pSS), and construct a nomogram model to predict LSGB results. A total of 181 patients who were admitted with suspected pSS from December 2018 to April 2023 were examined and divided into a training set (n = 120) and a validation set (n = 61). Baseline data of the two groups were examined, and the value of SGUS, MRI, and MRS in predicting LSGB was analyzed. Multivariate logistic analysis was used to screen for risk factors, and nomogram prediction models were constructed using these results. In the training set, the SGUS, MRI, and MRS scores of patients in the LSGB + group were higher than those in the LSGB - group (all P < 0.001). The positive prediction value (PPV) was 91% for an SGUS score of 3, and 82% for MRI and MRS scores of 2 or more. We developed a nomogram prediction model based on SGUS, MRI, and MRS data, and it had a concordance index (C-index) of 0.94. The Hosmer-Lemeshow test (χ2 = 3.17, P = 0.92) also indicated the nomogram prediction model had good accuracy and calibration for prediction of LSGB results. A nomogram model based on SGUS, MRI, and MRS results can help rheumatologists decide whether LSGB should be performed in patients with suspected pSS.

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.