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To investigate the abnormal characteristics of nailfold microcirculation (NMC) in patients with rheumatoid arthritis (RA) and to further analyze the associations between these abnormalities and common systemic inflammatory indicators or the key immunoregulatory cell subpopulation Th17/Treg cells. This cross-sectional observation study enrolled 120 RA patients as the RA group and 60 gender- and age-matched healthy individuals as the healthy control (HC) group. A NMC microscope was used to assess the NMC status and clinical data were collected. Spearman correlation was used to evaluate the relationships between NMC abnormalities and inflammatory or immunological indicators. Lasso regression and random forest model were used to screen key predictors. Receiver operating characteristic (ROC) curves were used to assess the diagnostic efficacy of the Th17/Treg ratio for moderate-to-severe NMC abnormalities, and the goodness-of-fit and clinical utility were validated using the Hosmer-Lemeshow test, calibration curves, and decision curve analysis (DCA). Bootstrap method was used for internal validation. Compared to the HC group, the RA group possessed higher number of crossed capillary loops, morphology score, flow pattern score, perivascular score, and total NMC score but lower flow velocity. Spearman correlation analysis demonstrated that the total NMC score was positively correlated with the platelet-to-lymphocyte ratio (PLR) (  = 0.028), platelet-to-red blood cell ratio (PAR) (  = 0.037), systemic immune-inflammation index (SII) (  = 0.009), and interleukin-2R (IL-2R) (  = 0.046). A total NMC score >4 was defined as moderate-to-severe NMC abnormality. Lasso regression and random forest model identified Th17/Treg ratio was the only independent associated factor for this subgroup and the area under the curve (AUC) was 0.708. The Hosmer-Lemeshow test and calibration curve confirmed favorable goodness-of-fit, and the DCA curve confirmed considerable clinical benefit of this model. The mean AUC from internal validation was 0.706, indicating satisfactory model stability. Our study illustrated the severity of NMC abnormality was significantly associated with systemic inflammatory burdens (PLR, PAR, SII) and core indicators of T-cell activation and dysfunction (IL-2R and Th17/Treg ratio).

Autoantibodies associated with systemic lupus erythematosus (SLE) are often present in patients with a variety of autoimmune diseases, affecting the diagnosis and differentiation of the diseases. In this study, the positive rates and diagnostic efficiencies of anti-dsDNA, anti-nucleosome, anti-ribosomal P and anti-C1q antibodies were analysed in 216 SLE patients, 323 rheumatoid arthritis (RA) patients, 87 Sjogren’s syndrome (SS) patients, 45 patients with other autoimmune diseases (OAD) and 52 healthy controls (HC). In addition to being high in SLE patients, the serum levels of anti-dsDNA and anti-nucleosome antibodies were also significantly higher in SS patients compared with OAD ( P  = 0.008, < 0.001). The ROC-AUCs for the four SLE-associated autoantibodies in distinguishing SLE patients from SS patients were lower than those in distinguishing SLE patients from HC. Therefore, SLE-associated autoantibody-positive SS patients represent a less studied and heterogeneous population, as these antibodies are also present in approximately 15% of all SS patients. Compared with SLE-associated autoantibody-negative SS patients, SS patients who were positive for SLE-associated autoantibodies were more likely to be positive for anti-nRNP/Sm autoantibodies (30.77% vs. 4.05%, P  = 0.001). Oral ulcerations, rampant dental and pulmonary involvement were more frequent in SS patients who were positive for SLE-associated autoantibodies than in those who were negative for these autoantibodies ( P  = 0.018, 0.004 and < 0.001). In conclusion, SLE-associated autoantibody-positive SS patients represent a heterogeneous population, characterized by unique autoantibody profiles and clinical manifestations. This study may provide new insights for diagnostic refinement between SLE and SS patients.

Double negative (DN) B cells, defined as CD27-IgD- B cells, are increased in older healthy individuals as well as in patients with certain diseases. However, the relationship between DN B cells and Sjögren’s disease (SjD) in newly diagnosed patients remains unclear. Seventy SjD patients and thirty-six healthy controls (HCs) were recruited in this study. Peripheral blood B cell subsets were analyzed using flow cytometry. The percentage and absolute count of DN B cells were significantly lower in SjD patients compared to HCs ( p = 0.000 and p = 0.007, respectively). Patients with medium to high disease activity, defined by an EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score ≥ 5, exhibited lower DN B cell levels compared to those with low disease activity (ESSDAI score < 5, p = 0.029 and p = 0.000, respectively). Moreover, lower DN B cell percentages were associated with glandular involvement ( p = 0.039) and neutropenia ( p = 0.034). Regression analysis revealed a negative correlation between DN B cells and SjD disease activity (B=-0.240, 95% CI:-0.468 to -0.013, p = 0.039). Additionally, DN B cells showed weak negative correlation with the percentage of total B cells ( r =-0.266, p = 0.026). This study demonstrates that DN B cells are decreased in SjD, particularly in patients with glandular involvement and high disease activity. Moreover, the inverse correlation between DN B cells and total B cells suggested that DN B cells may play a role in the pathogenesis of SjD.

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands. Our previous studies showed that myeloid-derived suppressor cells (MDSCs) exhibited impaired immunosuppressive function during disease progression in patients with SS and mice with experimental Sjögren’s syndrome (ESS), but it remains unclear whether restoring the function of MDSCs can effectively ameliorate the development of ESS. In this study, we found that murine olfactory ecto-mesenchymal stem cell-derived exosomes (OE-MSC-Exos) significantly enhanced the suppressive function of MDSCs by upregulating arginase expression and increasing ROS and NO levels. Moreover, treatment with OE-MSC-Exos via intravenous injection markedly attenuated disease progression and restored MDSC function in ESS mice. Mechanistically, OE-MSC-Exo-secreted IL-6 activated the Jak2/Stat3 pathway in MDSCs. In addition, the abundant S100A4 in OE-MSC-Exos acted as a key factor in mediating the endogenous production of IL-6 by MDSCs via TLR4 signaling, indicating an autocrine pathway of MDSC functional modulation by IL-6. Taken together, our results demonstrated that OE-MSC-Exos possess therapeutic potential to attenuate ESS progression by enhancing the immunosuppressive function of MDSCs, possibly constituting a new strategy for the treatment of Sjögren’s syndrome and other autoimmune diseases.

CD47 is overexpressed in many human cancers, its level positively correlates with tumor invasion and metastasis. However, it is largely unknown whether CD47 overexpression drives metastasis and how CD47 lead to tumor metastasis in non-small cell lung cancer (NSCLC). In this study, we analyzed NSCLC specimens and cell lines and revealed that CD47 is expressed at a higher level than in tumor-free control samples. Furthermore, increased CD47 expression correlated with clinical staging, lymph node metastasis and distant metastasis. In order to understand the molecular mechanisms underlying CD47 functions, we applied both gain-of-function and loss-of-function approaches in cell lines. The siRNA-mediated downregulation of CD47 inhibited cell invasion and metastasis in vitro , while the overexpression of CD47 by plasmid transfection generated opposite effects. In vivo, CD47-specific shRNA significantly reduced tumor growth and metastasis. On the molecular level, the expression of CD47 correlated with that of Cdc42, both in cell lines and NSCLC specimens. The inhibition of Cdc42 attenuates the invasion and metastasis of CD47-overexpressing cells. These results indicate that Cdc42 is a downstream mediator of CD47-promoted metastasis. Our findings provide first evidence that CD47 is an adverse prognostic factor for disease progression and metastasis and a promising therapeutic target for NSCLC.

Objectives: Articular manifestations have been reported in 19.3%–53.5% of patients with primary Sjogren’s syndrome. Our aim was to profile the clinical characteristics of Chinese patients with primary Sjogren’s syndrome who presented with articular manifestations at the time of initial treatment. Methods: We conducted a retrospective study of 129 primary Sjogren’s syndrome patients admitted to the second Affiliated Hospital of Dalian Medical University between April 2016 and December 2021 for initial treatment. Clinical and serological features, extra-articular involvement, and initial treatment were compared between primary Sjogren’s syndrome patients with and without articular manifestations. Results: Fifty-seven (44.2%) primary Sjogren’s syndrome patients had articular manifestations (mean age at diagnosis: 53.4 years), of which 42 (73.7%) presented with symmetrical distribution, 21 (36.8%) patients had rheumatoid factor positivity, and 11 (20.0%) patients had anti-cyclic citrullinated peptide antibodies positivity (mean 6.8 RU/mL); imaging examinations showed no signs of structural damage in these patients. The presence of articular manifestations showed positive correlation with anti-cyclic citrullinated peptide antibody level (odds ratio (OR) 1.01, 95% confidence interval (CI): 1.00–1.02; p = 0.049), C-reactive protein level (OR 1.15, 95% CI: 1.10–1.20; p = 0.000), and European League Against Rheumatism Sjogren syndrome disease activity index scores (OR 1.18, 95% CI: 1.11–1.25; p = 0.000). Ninety (69.8%) primary Sjogren’s syndrome patients received hydroxychloroquine therapy. Hydroxychloroquine treatment was significantly less frequently used in articular manifestation patients (35 (70.0%) vs 55 (85.9%); p = 0.038). Conclusions: Symmetrical polyarthritis was the most common clinical manifestation of primary Sjogren’s syndrome patients with articular manifestations in this cohort. Articular manifestations were associated with higher prevalence of C-reactive protein level, and European League Against Rheumatism Sjogren syndrome disease activity index score.

Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune disorders with unknown etiology. Despite the established link between gut microbes and immunity, the roles of gut bacteriome, mycobiome, and virome in IIM are unexplored. We performed shotgun metagenomic sequencing on fecal samples from 34 IIM patients and 37 healthy controls to profile gut microbiota. Taxonomic, functional, network, and machine-learning analyses revealed microbial dysbiosis and its potential for discriminating IIM. All three microbial kingdoms were significantly altered in IIM. Several inflammation-associated bacterial taxa (e.g., Rothia mucilaginosa , Streptococcus parasanguinis , Trueperella pyogenes ) and opportunistic fungi (e.g., Aspergillus spp.) were enriched in IIM, while SCFA-producing bacteria and fungi were depleted. Virome analysis revealed substantial shifts, with higher abundance of Siphoviridae in IIM. Altered viral functional gene profiles suggesting enhanced phage-mediated genome integration, recombination, and bacterial stress adaptation. Multi-kingdom network analysis showed extensive rewiring in IIM, characterized by increased network connectivity and a shift toward fungi-centered ecological hubs, contrasting with bacteria/virus-dominated networks in controls. In machine-learning models, the virome demonstrated the strongest discriminatory power, and viral signatures dominated the combined multi-kingdom classifier (AUC = 0.997). This first comprehensive multi-kingdom gut microbiota analysis in IIM provides a foundation for developing diagnostic and therapeutic strategies.

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disorder shaped by host genetics and environmental exposures, including the gut microbiota. While bacterial dysbiosis in SLE is well characterized, the role of the gut mycobiome and its cross-kingdom interactions remains largely unexplored. Methods Using fecal metagenomic sequencing from 117 SLE patients and 115 healthy controls (HCs), we established a non-redundant fungal genome catalog and revealed significant alterations in fungal composition, function, and cross-kingdom ecology. Results Fungal diversity was increased in SLE, with enrichment of potentially pathogenic taxa such as Candida , Malassezia , and Trichophyton , and depletion of commensal genera such as Pichia . Functional analysis showed expanded biosynthetic and redox capacities in SLE-associated fungi, including enrichment of RiPP- and terpene-related biosynthetic gene clusters and oxidative stress–related Pfam domains. Several predicted metabolites—such as kynurenine, phenylacetic acid, secondary bile acids, and acylcarnitines—were linked to immune activation and inflammation, suggesting that fungal metabolism may contribute to immune dysregulation. Network analysis revealed sparser and less centralized fungal–bacterial interactions in SLE, indicating disrupted ecological stability and the emergence of fungal taxa as key structural drivers. Integrating fungal and bacterial profiles markedly improved diagnostic performance (AUC = 0.934), underscoring the complementary predictive value of the gut mycobiome. In contrast, post-treatment samples showed reduced fungal richness but no major compositional shifts. Conclusions This study provides a comprehensive, multi-dimensional view of the gut mycobiome in SLE, demonstrating its taxonomic, functional, and ecological remodeling. Our findings highlight the potential contribution of fungal metabolic and redox activities to SLE pathogenesis and support the inclusion of fungi in multi-kingdom microbiome frameworks for disease diagnosis and therapeutic development.

Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis.

We investigated the relationship between inflammatory indicators derived from complete blood cell (CBC) counts and all-cause mortality in individuals with rheumatoid arthritis (RA). Data were collected from the National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2018, with a median follow-up duration of 78 months. The inflammatory indicators derived from CBC included several types: the systemic inflammatory response index (SIRI), the systemic immune-inflammation index (SII), the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the monocyte-to-lymphocyte ratio (MLR). The multiple COX regression models were used to estimate adjusted hazard ratios (HRs) and 95% CIs concerning all-cause mortality of participants with RA, which focused on CBC-derived inflammatory indicators. Additionally, restricted cubic spline (RCS) curve was utilized to investigate non-linear associations. The research comprised a cohort of 1,314 individuals, among whom 246 with RA succumbed during a median follow-up duration of 78 months. After adjusting for key covariates, the mortality rate in patients with RA who had high SIRI, NLR, and MLR levels was considerably higher than in those with medium or low SIRI, NLR, and MLR levels. Compared with the lowest tertile, the highest tertiles of SIRI (HR 1.87, 95% CI: 1.12-3.13), NLR (HR 1.79, 95% CI: 1.10-2.92), and MLR (HR 1.88, 95% CI: 1.17-3.02) were associated with an increased risk of all-cause mortality. The Kaplan-Meier analysis indicated a significant decrease in the survival probability among individuals with elevated SIRI, NLR, and MLR levels. The RCS analysis revealed a linear association between SIRI, NLR, MLR, and RA-related all-cause mortality, whereas a non-linear relationship was identified between the SII, PLR, and mortality. This investigation revealed that the SIRI, NLR, and MLR are novel, valuable, and convenient inflammatory indicators. In the United States adults with RA, higher SIRI, NLR, and MLR were independently associated with an increased long-term mortality risk. These findings not only assist in uncovering the potential utility of predicting RA outcomes but also provide rheumatologists valuable guidance for disease management.