Integrative analysis of transcriptome and proteome in primary Sjögren syndrome.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is a intricate autoimmune disease mainly characterized of immune-mediated destruction of exocrine tissues, such as salivary and lacrimal glands, occurring dry mouth and eyes. Although some breakthroughs in understanding pSS have been uncovered, many questions remain about its pathogenesis, especially the internal relations between exocrine glands and secretions. METHOD: Transcriptomic and proteomic analyses were conducted on salivary tissues and saliva in experimental Sjögren syndrome (ESS). The ESS model was established by immunization with salivary gland protein. The expression of mRNAs and proteins in salivary tissues and saliva were determined by high-throughput sequencing transcriptomic analysis and LC-MS/MS-based proteome, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to recognize dysregulated genes and proteins. The association between RNA and protein abundance was investigated to provides a comprehensive understanding of RNA-protein correlations in the pathogenesis of pSS. RESULTS: As a result, we successfully established the ESS model. We recognized 3221 differentially expressed genes (DEGs) and 253 differentially expressed proteins (DEPs). The sample analysis showed that 61 proteins overlapped through the integrative analysis of transcriptomics and proteomics data. The enrichment pathway analysis of DEGs and DEPs in samples showed alterations in renin-angiotensin-system (RAS), lysosome, and apoptosis. Notably, we found that some genes, such as AGT, FN1, Klk1b26, Klk1, Klk1b5, Klk1b3 had a consistent trend in the regulation at the RNA and protein levels and might be potential diagnostic biomarkers of pSS. CONCLUSION: Herein, we found critical processes and potential biomakers that may contribute to pSS pathogenesis by analyzing dysregulated genes and pathways. Additionally, the integrative multi-omics datasets provided additional insight into understanding complicated disease mechanisms.

Implications of IFNγ SNP rs2069705 in primary Sjögren's syndrome: transcriptional activation and B cell infiltration.

Primary Sjögren's syndrome (pSS) is characterized by its autoimmune nature. This study investigates the role of the IFNγ SNP rs2069705 in modulating the susceptibility to pSS. Differential expression of IFNγ and BAFF was analyzed using the GEO database's mRNA microarray GSE84844. Genotyping of the IFNγ SNP rs2069705 was conducted via the dbSNP website. The JASPAR tool was used for predicting transcription factor bindings. Techniques such as dual-luciferase reporter assays, Chromatin immunoprecipitation, and analysis of a pSS mouse model were applied to study gene and protein interactions. A notable increase in the mutation frequency of IFNγ SNP rs2069705 was observed in MNCs from the exocrine glands of pSS mouse models. Bioinformatics analysis revealed elevated levels of IFNγ and BAFF in pSS samples. The model exhibited an increase in both CD20+ B cells and cells expressing IFNγ and BAFF. Knocking down IFNγ resulted in lowered BAFF expression and less lymphocyte infiltration, with BAFF overexpression reversing this suppression. Activation of the Janus kinase (JAK)/STAT1 pathway was found to enhance transcription in the BAFF promoter region, highlighting IFNγ's involvement in pSS. In addition, rs2069705 was shown to boost IFNγ transcription by promoting interaction between its promoter and STAT4. SNP rs2069705 in the IFNγ gene emerges as a pivotal element in pSS susceptibility, primarily by augmenting IFNγ transcription, activating the JAK/STAT1 pathway, and leading to B-lymphocyte infiltration in the exocrine glands.NEW & NOTEWORTHY The research employed a combination of bioinformatics analysis, genotyping, and experimental models, providing a multifaceted approach to understanding the complex interactions in pSS. We have uncovered that the rs2069705 SNP significantly affects the transcription of IFNγ, leading to altered immune responses and B-lymphocyte activity in pSS.

VNN2-expressing circulating monocytes exhibit unique functional characteristics and are decreased in patients with primary Sjögren's syndrome.

OBJECTIVE: This study aims to elucidate the significance of VNN2 expression in peripheral blood monocytes and its clinical relevance in primary Sjögren's syndrome (pSS). METHODS: We investigated VNN2 expression by analyzing single-cell RNA sequencing (scRNA-seq) data from peripheral blood mononuclear cells. Flow cytometry was used to detect and compare VNN2 expression in total monocytes, classical monocytes (cMo), intermediate monocytes (iMo) and non-classical monocytes (ncMo). Additionally, we examined the expression of HLA, ICAM1, CD62L, ITGAM, S100A8, S100A9, CCR2, CCR6, CX3CR1 and CXCR3 in VNN2+ and VNN2- cells. We analyzed the correlation between VNN2 expression and clinical indicators and assessed the clinical utility of VNN2+ monocytes in pSS diagnosis using receiver operating characteristic curves. RESULTS: We observed high VNN2 expression in monocytes, with significantly higher levels in CD14++ monocytes compared to ncMo. VNN2+ monocytes exhibited decreased expression of HLA and CD62L and increased expression of ICAM1, ITGAM, S100A8, S100A9, CCR2, CCR6, CX3CR1 and CXCR3 compared to VNN2- monocytes. Although scRNA-seq data showed that VNN2 mRNA was upregulated, cell surface expression of VNN2 was decreased in monocytes from pSS patients compared to healthy controls. The reduced levels of VNN2+ monocyte subpopulations in pSS patients were negatively correlated with anti-ribosome antibody levels and positively correlated with complement 4 levels. Detection of VNN2 expression in monocytes can aid in the auxiliary diagnosis of pSS. CONCLUSION: Monocytes expressing cell surface VNN2 are significantly reduced in pSS patients. This suggests a potential role for VNN2 in pSS development and its potential use as a diagnostic marker for pSS.

Deep learning in the precise assessment of primary Sjögren's Syndrome based on ultrasound images.

OBJECTIVES: This study aimed to investigate the value of a deep learning (DL) model based on greyscale ultrasound (US) images for precise assessment and accurate diagnosis of primary Sjögren's syndrome (pSS). METHODS: This was a multicentre prospective analysis. All pSS patients were diagnosed according to 2016 ACR/EULAR criteria. 72 pSS patients and 72 sex- and age-matched healthy controls recruited between January 2022 and April 2023, together with 41 patients and 41 healthy controls recruited from June 2023 to February 2024 were used for DL model development and validation, respectively. DL model was constructed based on the ResNet 50, input with preprocessed all participants' bilateral submandibular glands (SMGs), parotid glands (PGs), and lacrimal glands (LGs) greyscale US images. Diagnostic performance of the model was compared with two radiologists. The accuracy of prediction and identification performance of DL model were evaluated by calibration curve. RESULTS: 864 and 164 greyscale US images of SMGs, PGs, and LGs were collected for development and validation of the model. The AUCs of DL model in the SMG, PG, and LG were 0.92, 0.93, 0.91 in the model cohort, and were 0.90, 0.88, 0.87 in the validation cohort respectively, outperforming both radiologists. Calibration curves showed the prediction probability of DL model were consistent with the actual probability in both model cohort and validation cohort. CONCLUSION: DL model based on greyscale US images showed diagnostic potential in the precise assessment of pSS patients in the SMG, PG, and LG, outperforming conventional radiologist evaluation.

A new insight on evaluation of the fertility and pregnancy outcome in patients with primary Sjögren syndrome: a propensity score matched study in multi-IVF centers.

BACKGROUND: Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it's currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it's unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. OBJECTIVE: This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. METHODS: We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. RESULTS: Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison. CONCLUSION: Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients.

A novel enzyme-linked immunosorbent assay tool to evaluate plasma soluble CD226 in primary Sjögren's syndrome.

CD226 is an important receptor constitutively expressed on most immune cells, performing vital functions in immune responses. However, the levels of soluble CD226 (sCD226) and its roles in primary Sjögren syndrome (pSS) remain unclear. In this study, we developed two novel mouse anti-human CD226 monoclonal antibodies (mAbs) and established a novel sandwich enzyme-linked immunosorbent assay (ELISA) system, which proved to be highly effective in detecting human sCD226. We then analyzed the expression of sCD226 in the plasma of pSS patients. Our results showed that the levels of sCD226 were significantly lower in patients with pSS compared to healthy controls. The significant decline was also observed in active group and the patients with high levels of IgG or positive anti-SSB. Additionally, reduced sCD226 was found to be negatively correlated with the disease activity of pSS and several clinical manifestations, including arthralgia, fatigue, decayed tooth and interstitial lung disease (ILD). Furthermore, receiver operator characteristics (ROC) curve analysis showed that sCD226 displayed outstanding capacity in discriminating pSS and predicting the disease activity. Altogether, plasma sCD226 emerges as a promising candidate for diagnostic markers in the context of pSS.

Gynecological symptoms in primary and secondary Sjögren's syndrome and the effect of the disease on sexuality.

BACKGROUND: Sjögren's syndrome (SS) is an autoimmune systemic disease affecting many organs and systems, such as genital system. AIM: This study aimed to present the gynecological symptoms of patients who were followed up in an outpatient clinic because of primary Sjögren's syndrome (pSS) and secondary Sjögren's syndrome (sSS) and to show how the disease affected sexuality. METHODS: This study is a cross-sectional study conducted between 2019 and 2020. The study sample consisted of 60 pSS patients, 42 sSS patients, and 52 healthy control subjects. OUTCOMES: All the participants were questioned about sexuality, and completed the 36-item Short Form Survey, Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, and Modified Hill questionnaire. RESULTS: The patients had a mean age of 55.6 ± 11.85 years in pSS, 59.39 ± 11.18 years in sSS, and 56.1 ± 10.46 years in healthy control subjects. Vaginal and vulvar dryness and dyspareunia were present at a significantly higher rate in SS, especially in pSS, compared with the control subjects. The Health Assessment Questionnaire score was significantly lower in the pSS group than in the sSS group. Arthralgia, myalgia, and fatigue were prominent in all SS patients. CLINICAL IMPLICATIONS: Gynecological symptoms, sexual ability, and the effects of the disease on sexuality should be questioned in all SS patients. STRENGTHS AND LIMITATIONS: It is very important that we evaluate the gynecological symptoms of both pSS and sSS patients and the effect of the disease on these symptoms. The small number of patients and healthy control subjects is a limitation. CONCLUSION: The gynecological and musculoskeletal symptoms negatively affected sexuality in patients with pSS and sSS, and the negative effect of the disease on sexuality was more pronounced in the pSS group.

Neurological and Psychiatric Clinical Manifestations of Sjögren Syndrome.

PURPOSE OF REVIEW: Sjögren Syndrome is a systemic autoimmune disorder that presents mainly with sicca symptoms, but frequently affects other body systems which can lead to a wide variety of manifestations. Understanding the neurological and psychiatric manifestations of Sjögren Syndrome can help with an earlier diagnosis of this disease and leads to better clinical outcomes. RECENT FINDINGS: We provide an updated overview of the central neurological manifestations, peripheral neurological manifestations and psychiatric manifestations and their diagnosis when associated with primary Sjögren Syndrome. The epidemiology and clinical features of the neurological and psychiatric manifestations are derived from different cohort studies and review articles that were selected from PubMed searches conducted between January 2024 and March 2024. The absence of diagnostic criteria and the scarcity of large, robust studies makes the recognition of the neurological and psychiatric manifestations of Sjögren Syndrome more difficult. Maintaining a high index of suspicion in clinical practice and a close collaboration between the Neurologist and the Rheumatologist will facilitate the diagnosis and management of these patients.

Kidney manifestations of pediatric Sjögren's syndrome.

Approximately 1% of all patients with Sjögren's syndrome (SS) are children. Unlike the adult form, in which sicca syndrome is the main presentation, in children, the most common clinical finding is recurrent enlargement of the salivary glands. In pediatric SS, extraglandular manifestations represent a significant feature and, among these, kidney manifestations are relevant. Kidney involvement is observed in 5-20.5% of children with SS, most frequently tubulointerstitial nephritis. This injury can lead to serious phenotypes, including distal kidney tubular acidosis with the development of severe hypokalemia, which can lead to ECG abnormalities, weakness, and hypokalemic periodic paralysis. Kidney implications in pediatric SS also include nephrolithiasis, nephrocalcinosis, and various types of glomerular damage, which often require immunosuppressive therapies. Laboratory findings are usually comparable to adults, including hyperglobulinemia and high rates of antinuclear antibodies (ANA, 63.6-96.2%), and anti-Ro/SSA (36.4-84.6%). The current classification criteria for SS are inaccurate for the pediatric population, and more specific criteria are needed to improve the diagnostic rate. Due to the rarity of the disease, strong recommendations for treatment are lacking, and several therapeutic strategies have been reported, mostly based on glucocorticoids and disease-modifying antirheumatic drugs, with different outcomes. The aim of this paper is to provide an overview of the kidney implications of pediatric SS based on the latest evidence of the medical literature.

Causal relationship between multiple sclerosis and primary Sjögren's syndrome: a two-sample mendelian randomization study.

This study aims to investigate the causal relationship between primary Sjögren's syndrome (SS) and multiple sclerosis (MS) using a two-sample Mendelian randomization (MR) analysis to provide insights into their common mechanisms and implications for therapeutic strategies. We utilized data from Genome-Wide Association Studies (GWAS) for primary SS (1,290 cases and 213,145 controls) and MS (4,888 cases and 10,395 controls), restricted to European ancestry. Instrumental variables (IVs) were selected based on genetic variants associated with primary SS. The primary MR method was Inverse Variance Weighted (IVW), supplemented by MR Egger, Weighted Median, Simple Mode, and Weighted Mode algorithms to assess the bidirectional causal relationships between MS and primary SS. Sensitivity analyses, including MR-PRESSO and leave-one-out analysis, were conducted to ensure the robustness of our findings. After excluding SNPs with pleiotropic effects, 42 and 5 SNPs were identified as robust IVs for primary SS and MS, respectively. Our analysis revealed a significant protective effect of MS on primary SS, with IVW showing an OR of 0.896 (95% CI: 0.841-0.954, P = 0.001). No significant heterogeneity or horizontal pleiotropy was detected, supporting the reliability of the results. Our findings suggest a potential protective effect of MS against primary SS, indicating a negative causal association between these two autoimmune diseases. This adds valuable genetic evidence to the understanding of the complex interplay between primary SS and MS, offering new avenues for research and therapeutic interventions.

Clinical Performance of Immunonephelometric Assay and Chemiluminescent Immunoassay for Detection of IgG Subclasses in Chinese.

BACKGROUND: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc. METHODS: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820). CONCLUSIONS: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice.

Nephrolithiasis and/or nephrocalcinosis is significantly related to renal dysfunction in patients with primary Sjögren's syndrome.

OBJECTIVE: The present study compared the clinical features of patients with primary Sjögren's syndrome (pSS) with and without nephrolithiasis and/or nephrocalcinosis to determine factors related to renal dysfunction. METHODS: The clinical features of 68 patients with anti-Sjogren's syndrome antigen A (SSA)/Ro-antibody-positive pSS with and without nephrolithiasis and/or nephrocalcinosis who underwent abdominal computed tomography and/or ultrasonography were retrospectively analysed. RESULTS: Of the 68 patients with anti-SSA-antibody-positive pSS, 23 (33%) had renal nephrolithiasis and/or nephrocalcinosis, whereas 45 (67%) did not. Fourteen (20%) patients had renal dysfunction at diagnostic imaging. Among five patients who underwent renal biopsy, four patients with renal nephrolithiasis and/or nephrocalcinosis were diagnosed with tubulointerstitial nephritis, and one without nephrolithiasis and/or nephrocalcinosis was diagnosed with minimal change nephrotic syndrome. Estimated glomerular filtration rate at diagnostic imaging was significantly lower in patients with than without nephrolithiasis and/or nephrocalcinosis group (P = 0.010). In addition to nephrolithiasis and/or nephrocalcinosis (odds ratio [OR], 3.467; P = 0.045), the gap between serum sodium and chloride concentrations (OR, 10.400; P = 0.012) and increased urinary ß2-microglobulin (OR, 5.444; P = 0.033) were associated with renal dysfunction at the time of diagnostic imaging. CONCLUSION: Nephrolithiasis and/or nephrocalcinosis, normal anion gap metabolic acidosis, and tubulointerstitial damage are associated with renal dysfunction in patients with pSS.

Relationships between inflammation markers and the risk of hypertension in primary Sjögren's syndrome: A retrospective cohort study.

OBJECTIVES: The association of inflammation markers with hypertension (HTN) in primary Sjögren's syndrome (pSS) remains controversial. We aimed to investigate whether inflammation markers are at increased risk of developing HTN in pSS patients. METHODS: A retrospective cohort study included pSS patients (n = 380) between May 2011 and May 2020 from the Third People's Hospital of Chengdu. Multivariable Cox regression analyses were used to estimate hazard ratios (HRs) of the potential inflammation markers for pSS-HTN. Subsequently, the dose-response relationships were also used. RESULTS: Out of 380 pSS patients, 171 (45%) developed HTN, and the median follow-up period was 4.16 years. Univariable Cox regression analysis showed that the erythrocyte sedimentation rate (ESR) and neutrophils were significantly associated with the incident HTN (P < 0.05). After adjustment for covariates, this association between ESR (adjusted HR 1.017, 95%CI: 1.005-1.027, P = .003), neutrophils (adjusted HR 1.356, 95%CI: 1.113-1.653, P = .003), and HTN remained significant. The dose-effect relationship was also found between ESR, neutrophils, and HTN (P = .001). CONCLUSIONS: Inflammation markers may play an important role in the incident HTN in pSS.

Systematic review and meta-analysis of the diagnostic performance of lacrimal gland ultrasound elastography in primary Sjögren's syndrome.

OBJECTIVE: This research conducted a comprehensive evaluation of the effectiveness of ultrasonic elastography (USE) in detecting lacrimal gland involvement in individuals suffering from primary Sjögren's syndrome (pSS). METHODS: A comprehensive search was undertaken across multiple databases including PubMed, the Cochrane Library, EMBASE, Wanfang, Web of Science, and the Chinese National Knowledge Infrastructure, to gather relevant literature pertaining to the application of USE in diagnosing pSS from January 1, 2000, to October 1, 2023. Pooled data were used to calculate sensitivity, specificity, and diagnostic odds ratios. Several summary metrics were used to evaluate SWE's performance in detecting pSS, including the area under the receiver operating characteristic curve, diagnostic odds ratios, sensitivities, and specificities. RESULTS: Five pertinent studies included a total of 273 patients. Shear wave elastography (SWE) demonstrated a pooled sensitivity of 0.88 (95% CI 0.77-0.94) and specificity of 0.94 (95% CI 0.88-0.98), with an area under the receiver operating characteristic curve of 0.97 (95% CI 0.95-0.98). SWE exhibited a positive likelihood ratio of 15.86 (95% CI 6.99-36.00) and a negative likelihood ratio of 0.13 (95% CI 0.07-0.25). No evidence of publication bias was observed (p = 0.70). CONCLUSION: SWE demonstrates a remarkable degree of precision in detecting lacrimal gland involvement in individuals suffering from pSS.

Choroidal, retinal, and optic nerve changes in rheumatoid arthritis and primary sjogren's syndrome patients: comparison with each other and healthy subjects.

PURPOSE: The present study aims to evaluate the optic nerve, macula, and choroidal changes in both rheumatoid arthritis (RA) and primary Sjögren's syndrome (SjS) patients, and to compare these findings with age-matched healthy volunteers. METHODS: This study included 46 RA patients, 33 primary SjS patients, and 37 age-matched healthy volunteers. All of the patients underwent a thorough ophthalmological examination, during which measurements of the retinal nerve fiber layer (RNFL), ganglion cell layer(GCL), and subfoveal choroidal thickness (CT) were taken using OCT (optical coherence tomography). The measurements taken from the right eye of each patient were used to compare among the groups. RESULTS: RNFL thickness in superior quadrant was found to be statistically significantly thinner in the eyes with RA when compared to the control group (p = 0.022). In the nasal quadrant, the RNFL thickness was significantly thinner in patients with primary SjS compared to healthy individuals (p = 0.036). Also, the temporal quadrant RNFL was significantly thinner in RA patients than in the primary SjS patients (p = 0.033). GCL thickness was observed to be thinner in all quadrants of both RA and primary SjS groups compared to the control group. However, the difference was not found to be statistically significant. Subfoveal CT was observed to be thicker in RA and SjS groups compared to the control group, but this difference was also not statistically significant. CONCLUSION: Systemic autoimmune diseases like RA and primary SjS can lead to a decrease in RNLF and GCL thickness, which can impair visual acuity even in the absence of ocular symptoms. Therefore, monitoring changes in the optic nerve, retina, and choroid layer are crucial in these patients.

Risk factors of primary Sjögren's syndrome combined with osteoporosis. / åŽŸå‘æ€§å¹²ç‡¥ç»¼åˆå¾åˆå¹¶éª¨è´¨ç–æ¾çš„å±é™©å› ç´ .

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is prevalent in middle-aged and elderly women, characterized by dry mouth, dry eyes, fatigue, and joint pain. Nearly one-third pSS patients have been suffering with osteoporosis (OP), displaying symptoms of lumbago, back pain, and even fracture, all of which severely affect their life quality. Common risk factors for pSS and OP include gender and age, persistent state of inflammation, immune disorders, intestinal flora imbalance, vitamin D deficiency, dyslipidemia and sarcopenia. Meanwhile, the comorbidities of pSS, such as renal tubular acidosis, primary biliary cholangitis, autoimmune thyroid diseases, and drugs (glucocorticoids, methotrexate, and cyclophosphamide) are unique risk factors for pSS complicated with OP. Education, guidance of healthy lifestyle, and OP screening are recommended for bone management of pSS patients. Early detection and intervention are crucial for keeping bone health and life quality in pSS patients.

mTORC1-GLUT1-mediated glucose metabolism drives hyperactivation of B cells in primary Sjogren's syndrome.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by B cell hyperactivation and hypergrammaglobulinemia. Currently, the role of metabolic pathways in the B cells of pSS patients is poorly defined. Here, we showed that upon cytosine phosphate-guanine (CpG)/sCD40L/IL-4 stimulation, B cells proportionally increased glycolysis and oxygen consumption, and compared with B cells from healthy controls (HCs), B cells from pSS patients exhibited higher glycolysis capacity and maximal oxidative respiration (OXPHOS). We also found that glucose transporter 1 (GLUT1) expression in B cells from pSS patients was significantly higher than that in B cells from HCs. Treatment with 2-deoxy-d-glucose (2-DG) inhibited the activation of B cells in pSS patients. Both 2-DG and Metformin inhibited the proliferation, formation of plasma/plasmablasts and decreased the IgG and IgM levels in the supernatants of B cells from pSS patients. Furthermore, inhibition of mTORC1 by rapamycin had an effect similar to that of 2-DG, suppressing B cell activation, proliferation and antibody production. Taken together, we demonstrated that B cells from pSS patients are more metabolically active than those from HCs and suggested that the mTORC1-GLUT1 glycolysis pathways were the major drivers of B cell hyperactivation and autoantibody production in pSS patients.

The decreased of peripheral blood natural killer cell is associated with serum IL-2 level in the renal tubular acidosis in patients with primary sjogren's syndrome.

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.

Non-invasive diagnosis of primary Sjögren's syndrome using ultrasonography and transcriptome biomarkers.

Diagnosing primary Sjögren's syndrome (pSS) is difficult due to clinical heterogeneity and the absence of non-invasive specific biomarkers. To develop non-invasive pSS diagnosis methods that integrate classic clinical indexes, major salivary gland ultrasonography (SGUS), and gene expression profiles shared by labial gland and peripheral blood, we conducted a study on a cohort of 358 subjects. We identified differentially expressed genes (DEGs) in glands and blood that were enriched in defense response to virus and type I interferon production pathways. Four upregulated DEGs common in glands and blood were identified as hub genes based on the protein-protein interaction networks. A random forest model was trained using features, including SGUS, anti-SSA/Ro60, keratoconjunctivitis sicca tests, and gene expression levels of MX1 and RSAD2. The model achieved comparable pSS diagnosis accuracy to the golden standard method based on labial gland biopsy. Our findings implicate this novel model as a promising diagnosis technique of pSS.

Compositional and functional aberrance of the gut microbiota in treatment-naïve patients with primary Sjögren's syndrome.

OBJECTIVES: To investigate the compositional and functional characteristics of the gut microbiota in primary Sjögren's syndrome (pSS) and compare them with those in systemic lupus erythematosus (SLE). METHODS: Stool samples from 78 treatment-naïve pSS patients and 78 matched healthy controls were detected by shotgun metagenomic sequencing and compared with those from 49 treatment-naïve SLE patients. The virulence loads and mimotopes of the gut microbiota were also assessed by sequence alignment. RESULTS: The gut microbiota of treatment-naïve pSS patients had lower richness and evenness and showed a different community distribution than that of healthy controls. The microbial species enriched in the pSS-associated gut microbiota included Lactobacillus salivarius, Bacteroides fragilis, Ruminococcus gnavus, Clostridium bartlettii, Clostridium bolteae, Veillonella parvula, and Streptococcus parasanguinis. Lactobacillus salivarius was the most discriminating species in the pSS patients, especially in those with interstitial lung disease (ILD). Among the differentiating microbial pathways, the superpathway of l-phenylalanine biosynthesis was also further enriched in pSS complicated with ILD. There were more virulence genes carried by the gut microbiota in pSS patients, most of which encoded peritrichous flagella, fimbriae, or curli fimbriae, three types of bacterial surface organelles involved in bacterial colonization and invasion. Five microbial peptides with the potential to mimic pSS-related autoepitopes were also enriched in the pSS gut. SLE and pSS shared significant gut microbial traits, including community distribution, altered microbial taxonomy and pathways, and enriched virulence genes. However, Ruminococcus torques was depleted in pSS patients but enriched in SLE patients compared to healthy controls. CONCLUSIONS: The gut microbiota in treatment-naïve pSS patients was disturbed and shared significant similarity with that in SLE patients.