Primary Sjögren disease (SjD) is a systemic autoimmune disease characterized by inflammation of exocrine glands, most commonly leading to dry mouth and dry eyes. Although the etiology of SjD remains unclear, emerging evidence suggests that the microbiome modulates immune homeostasis. This study aimed to compare the skin microbiomes of SjD patients with those of healthy controls (HCs) using 16S rRNA gene sequencing. Taxonomic composition, alpha and beta diversity, and predicted functional profiles were evaluated. We observed a significant depletion of Cutibacterium and a marked reduction in microbial diversity in SjD patients. Beta diversity analyses revealed distinct clustering among groups. Functional prediction suggested the downregulation of metabolic pathways associated with microbial homeostasis. Our findings propose that alterations in the skin microbiota may contribute to SjD pathogenesis and serve as potential biomarkers or therapeutic targets.

Primary Sjögren disease (pSS) is an autoimmune disease characterized primarily by predominant lymphocytic infiltration of the exocrine glands. While the etiopathogenesis of pSS remains unclear, current therapeutic strategies lack efficacy. In human submandibular gland epithelial cells (HSGECs), endoplasmic reticulum stress (ERS) induces apoptosis, leading to the cellular redistribution of Ro52/SSA autoantigens, the activation of the immune system, and the production of a large number of autoantibodies. Cells initiate autophagy to resist cellular damage caused by ERS and restore the normal physiological status. The ERK1/2-mTOR-autophagy signaling pathway has been implicated in numerous pathological conditions. In this study, an experimental Sjögren disease (ESS) mouse model was established to evaluate reduced protein levels and altered intracellular distribution of Ro52/SSA autoantigens through modulation of ERS and the ERK1/2-mTOR-autophagy pathway, resulting in diminished autoantibody production and ameliorated ESS symptoms. These findings provide an experimental foundation for therapeutic strategies targeting Ro52/SSA production in pSS.

To evaluate the diagnostic concordance between salivary gland ultrasound (SGUS) and minor salivary gland biopsy (MSGB) in suspected primary Sjögren disease (SjD), and to assess the added value of Doppler ultrasound and extended histopathologic features beyond the focus score (FS). We retrospectively analyzed 128 patients who underwent both SGUS and MSGB during diagnostic evaluation for SjD. SGUS was graded using the OMERACT system; MSGB was assessed for FS and additional features including fibrosis, atrophy, ductal dilatation, and lymphoepithelial lesions (LELs). The final clinical diagnosis was determined by expert rheumatologists. Diagnostic accuracy, concordance (Cohen's κ), and receiver operating characteristics (ROC) were analyzed. Of 128 patients, 95 were diagnosed with SjD. The overall SGUS-MSGB concordance rate was 67.2% (κ = 0.334). Among discordant cases, patients with positive biopsy but negative SGUS (n = 23) had a significantly higher SjD diagnosis rate than those with positive SGUS but negative biopsy (n = 19) (95.7% vs. 68.4%; OR = 10.15, p = 0.034). FS ≥ 1 had the highest diagnostic accuracy (AUC = 0.853), while adding extended features did not improve performance. Doppler ultrasound failed to enhance diagnostic accuracy, particularly in grayscale SGUS-negative patients. In MSGB-negative patients, SGUS positivity, anti-Ro/SSA antibody, and histologic fibrosis were independently associated with SjD. SGUS and MSGB demonstrate only fair diagnostic concordance and reflect complementary aspects of glandular involvement. Doppler ultrasound and extended histologic features provide limited incremental value. Key Points • In suspected primary SjD, SGUS and MSGB demonstrate modest agreement (κ = 0.334), with a 32.8% discordance rate. • MSGB with focus score ≥ 1 demonstrated the highest diagnostic accuracy, while extended histologic features (fibrosis, atrophy, LEL) did not provide additional diagnostic value. • Doppler ultrasound failed to improve diagnostic accuracy, especially in patients with structurally normal glands on grayscale SGUS (OMERACT grade 0-1). • In MSGB-negative patients, SGUS positivity, anti-Ro/SSA antibody, and histologic fibrosis were independently associated with expert-diagnosed SjD, supporting a complementary diagnostic approach.

The purpose of this study is to investigate the differences in the ocular signs and in vivo confocal microscope (IVCM) findings between dry eye disease (DED) patients with and without primary Sjögren disease (SjD), and to establish a predictive model to evaluate the serological activity of SjD based on IVCM findings: we examined 42 (84 eyes) and 41 (82 eyes) with and without SjD, respectively. IVCM was used to evaluate corneal nerve density (CND) and corneal dendritic cell density (DCD). Tear meniscus height (TMH), and tear film breakup time (BUT), corneal fluorescein staining (FL), serum anti-Ro/anti circular single stranded DNA antibody, anti-La/anti single chain binding protein antibody, IgG, C3, and salivary gland biopsies were performed. Patients with SjD had a lower CND (P < .0001), lower TMH (P < .001), higher DCD (P < .001), and higher corneal FL scores (P = .014) than patients without SjD. The equation for the prediction of SjD was as follows: Y1 = 4.313 + (-0.23) × CND + 0.02 × DCD + -10.89 × TMH (P < .0001). The negative and positive predictive powers of the model were 83.78% and 80.56%, respectively, and the cutoff value for Y1 was 0.392. The predicted serological activity of SjD was as follows: Y2 = -1.271 + 0.014 × DCD + 0.6074 × FL (P = .0002). The negative and positive predictive powers of the model were 68.75% and 84.38%, respectively. The cutoff value of Y2 was 0.427. CND, DCD, and TMH demonstrated good predictive values for distinguishing whether DED is caused by SjD. DED and FL had good predictive values for evaluating the serological activity of SjD.