The newly discovered Treg subset (CLA+ Tregs) expressing cutaneous lymphocyte-associated antigen is associated with inflammatory conditions. This study elucidated the role of CLA+ Tregs in rheumatoid arthritis (RA) development and its responses to treatment. A total of 12 T cell subsets, together with total T cells, B cells, and NK cells were analyzed in 169 patients with RA and 114 healthy controls using flow cytometry. Autoantibodies were detected by ELISA. The logistic regression models were employed to assess the association between cell subsets and rheumatoid arthritis. Relationships between CLA+ Tregs and clinical variables were assessed. Among the immune cell subsets analyzed, CLA⁺ Tregs were the most significantly reduced ones in patients with RA compared with healthy controls (OR 0.825 [0.764–0.891], p < 0.001). Decreased CLA⁺ Tregs were strongly correlated to active disease status (adjusted OR 0.814 [0.733–0.902], p = 0.004; AUC 0.916 [0.869–0.963], p < 0.001). Decreased CLA+ Tregs were associated with higher swollen joint count, tender joint count and DAS28 scores, as well as systemic involvements, including interstitial lung disease (ILD), anemia, fever, and skin vasculitis. Additionally, rheumatoid factor (RF) and anti-mutated citrullinated vimentin antibody (anti-MCV) were correlated to lower CLA+ Tregs. Compared to baseline prior treatment, CLA+ Tregs increased significantly in RA patients, accompanied by improvements in disease activity (median, 9.60

Behçet’s syndrome (BS), a chronic vasculitis, leads to recurrent oral ulcers, severely impacting quality of life. Here we report the results of a randomized, double-blind, placebo-controlled trial (NCT04065672) to evaluate the efficacy and safety of low-dose interleukin-2 (LD-IL-2) in BS patients. 60 participants with active oral ulcers are randomly assigned to receive LD-IL-2 or placebo. The primary endpoint is the oral ulcer count at week 12. The LD-IL-2 group has significantly fewer oral ulcers than the placebo group (0.69 ± 1.05 vs. 1.57 ± 0.90, P = 0.001) with greater improvements in ulcer pain, disease activity, and quality of life. No infections or severe adverse events are observed in either group. LD-IL-2 expands regulatory T (Treg) cells and decreased the ratio of effector T cell to Treg cells. Thus, LD-IL-2 therapy might be an effective and safe treatment in BS patients and is associated with the modulation of CD4 + T cell populations. Behçet’s syndrome is a chronic inflammatory disease with oral ulcers being the most common symptom. Here authors present results from a phase 2 randomized double-blind placebo-controlled clinical trial that shows that systemic low dose interleukin-2 could be safely administered to these patients, and the therapy may improve their quality of life.

Low-dose interleukin 2 (Ld-IL2) has shown therapeutic effects in autoimmune diseases, particularly systemic lupus erythematosus (SLE), yet optimal dosage has not been established in clinical trials. In this multicentre, double-blind, phase IIb trial, 152 patients with active SLE were randomised (1:1:1:1) to receive subcutaneous IL2 (0.2, 0.5, or 1.0 million IU) or placebo every other day for 12 weeks, then weekly for another 12 weeks. At week 12, SRI-4 response rates were higher in the IL2 1 M IU (69.7%), 0.5 M IU (64.7%), and 0.2 M IU (42.9%) groups than the placebo control group (23.5%). Notably, these differences persisted until week 24 (P < 0.001). Moreover, achievement of LLDAS increased in a dose-dependent manner. Patients who received 1 M IU also showed significant reductions in PGA scores, anti-dsDNA antibody titres and prednisone dosages. Infection rates were lower in the IL2 groups compared with placebo. Ld-IL2 drove the expansion of regulatory T cells (Tregs) and altered Treg/effector T cell ratios. These findings highlight the dose-dependent efficacy of IL2 with a favourable safety profile. (Clinicaltrials.gov registration number: NCT04077684).

Background Mucosal-associated invariant T (MAIT) cells are activated by microbe-derived metabolites and enriched at mucosal barriers, linking their biology closely to the gut microbiota. In rheumatoid arthritis (RA), MAIT-microbiota interactions may represent an underexplored pathogenic axis. Methods Peripheral blood MAIT cells were analysed by flow cytometry in 36 RA patients and 31 healthy controls (HCs). Fecal samples underwent 16S rRNA gene sequencing to characterize gut microbiota composition and PICRUSt2-based functional prediction analysis was performed to explore microbial metabolic pathways. Associations between microbial taxa, MAIT cells and clinical parameters were evaluated by non-parametric statistics and Spearman analysis. Results Circulating MAIT cells were significantly reduced in RA, particularly the loss of CD8⁺MAIT cells ( P < 0.01), and were further decreased in patients with moderate and high disease activity (M-HDA) ( P > 0.05). Compared to HCs, RA patients exhibited reduced gut microbial richness and diversity. Moreover, reduced genera Subdoligranulum , Parasutterella and Alloprevotella correlated positively with total and CD8⁺MAIT cells, whereas increased genus Eggerthella correlated negatively ( P < 0.05). Functional prediction revealed enriched genes ( ssuE , ribA/RIB1 , ribF , nudJ , RIB7 ) of riboflavin biosynthesis pathways in RA, with RIB7 expression significantly correlated with MAIT cell frequency ( P = 0.004). Conclusion RA is characterized by concurrent MAIT-cell depletion and gut microbiota dysbiosis, with specific microbial taxa linked to MAIT-cell alterations. The enrichment of riboflavin-pathway genes suggests a potential mechanism connecting microbial metabolism to MAIT-cell dysregulation. These findings support a microbiota–MAIT axis in RA pathogenesis and highlight potential targets for therapeutic intervention.

IgG4-related disease (IgG4-RD) is an immune-mediated condition with diagnostic challenges in clinical practice. Sensitive biomarkers are needed for diagnosis, disease activity and disease progression assessment. This study aimed to identify and validate novel serum protein biomarkers of IgG4-RD to improve clinical management. Using Olink proteomics, we analyzed the expression of 92 serum immuno-oncology-related proteins in 11 treatment-naïve IgG4-RD patients and 11 healthy controls (HCs). Candidate biomarkers capable of distinguishing IgG4-RD patients from HC were subsequently validated by enzyme-linked immunosorbent assay in a large independent cohort (n = 220). Diagnostic performance was assessed via 5-fold cross-validation. Correlations between biomarkers and clinical characteristics were also investigated, as well as predictive value for disease relapse. Olink proteomic analysis identified 27 differentially expressed proteins between IgG4-RD and HCs. Through longitudinal follow-up, serum PD1, OX40, CCL19, and MMP12 were significantly upregulated in IgG4-RD patients and closely associated with disease progression, serum IgG4 levels and inflammatory indicators. A comprehensive diagnostic model incorporating the four biomarkers was developed and showed high discriminatory capacity. Elevated baseline PD1 level served as an independent risk factor to predict clinical relapse of IgG4-RD patients. This study identifies four novel serum biomarkers that effectively assist diagnosis, assess disease activity, and one capable for clinical relapse prediction. These findings provide a practical approach for large-scale clinical screening and monitoring of IgG4-RD patients. Furthermore, the identified proteins may offer new insights into disease pathogenesis and represent potential therapeutic targets for this challenging condition.

CD161⁺ regulatory T cells (Tregs) are involved in rheumatoid arthritis (RA) pathogenesis. This study aimed to investigate the levels of circulating CD161⁺ Tregs in RA patients and to evaluate their associations with clinical features, laboratory indicators, and therapeutic responses. A total of 172 RA patients meeting the 2010 ACR/EULAR criteria and 110 age- and sex-matched healthy controls (HCs) were enrolled. The proportion of CD161⁺ Tregs in peripheral blood was quantified by flow cytometry. Correlations between CD161⁺ Treg levels and clinical manifestations, laboratory parameters, and disease activity scores (DAS28) were assessed. Twenty-four RA patients were longitudinally followed to assess post-treatment changes in CD161⁺ Tregs and disease activity. The proportions of CD161⁺ Tregs of the total Treg and CD4⁺ T cell populations were significantly elevated in RA patients compared to HCs (P < 0.001). Higher CD161⁺ Treg levels were associated with smoking history (P = 0.033) and inversely correlated with the presence of dry eye sicca (P = 0.030). These subsets showed positive correlations with IgA, IgM, rheumatoid factor (RF), RF-IgG, TNF-α+CD4+ T cell, Th17 and DAS28-ESR (P < 0.05), while exhibiting negative correlations with naïve Th cells and effector T (Teff) cells (P < 0.05). CD161⁺ Treg levels were higher in patients with long-standing RA (LRA) than in HCs (P < 0.05), and in patients with high disease activity (DAS28-ESR > 5.1) compared to those with moderate/low disease activity (P < 0.05). After treatment, decreased CD161⁺ Treg and disease activity scores were observed (P < 0.05), which were particularly pronounced in the group receiving csDMARDs combined with tocilizumab (an IL-6 inhibitor). However, csDMARDs alone or in combination with JAK inhibitors showed no or only partial efficacy. CD161⁺ Tregs are elevated in RA and associated with disease activity and immunologic indicators. CD161⁺ Tregs might serve as a biomarker for assessing RA disease activity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovitis. Synovial fibroblasts (SF) are the predominant cellular components in the inflamed synovium. Recent studies have shown increased expression of P2X7 receptor (P2X7R) in RA SF. However, its precise expression patterns and its contribution to inflammatory arthritis remain unclear. We demonstrate that P2X7R is robustly expressed in RA synovium, correlating with increased synovitis and systemic inflammation. Single-cell transcriptome analysis indicated that P2X7R was enriched in specific SF associated with refractory RA. Then, we applied a highly selective human P2X7R antagonist, EVT-401, which promoted apoptosis and induced cell cycle arrest in RA SF, reduced the production of proinflammatory and joint-destructive mediators, and mitigated aggressive phenotypes. Furthermore, we demonstrated that EVT-401 markedly reduced synovial inflammation and arthritis severity in a nonhuman primate model of autoimmune arthritis. Together, these findings suggest that P2X7R is involved in synovial inflammation and its inhibition may represent a potential therapeutic strategy for refractory RA.

This study aimed to use machine learning to explore Behçet’s syndrome (BS) heterogeneity by integrating immunocyte subpopulations and clinical characteristics. We prospectively enrolled BS patients and recorded their demographic and clinical characteristics. Various peripheral immune cells were analysed using flow cytometry. Unsupervised machine learning was used to perform cluster analysis based on the clinical manifestations and immune cell subsets. Patients were followed up for one year to evaluate treatment response and remission rates. RNA sequencing was performed in patients with clustered BS and healthy controls. Unsupervised machine learning categorized 201 BS patients into four clusters with distinct clinical and immunological features. Cluster 1 showed isolated mucocutaneous lesions, low inflammation, and high remission, with transcriptomic enrichment in IFN-γ, IL-6, and JAK-STAT pathways. Cluster 2 featured arthritis, elevated inflammatory levels, and responded well to TNF-α inhibitors, with transcriptomic enrichment in TNF and B-cell activation pathways. Cluster 3 had cardiovascular involvement, reduced CLA+ Tregs, and also responded to TNF-α inhibitors, with transcriptomic enrichment in coagulation, platelet activation, and MAPK pathways. Cluster 4 demonstrated neurological involvement, elevated CD161⁺ Tregs, low remission, and a better response to mycophenolate mofetil, with transcriptomic enrichment in T-cell activation and NF-κB pathways. Unsupervised clustering of BS patients revealed four distinct subtypes with significant clinical and immunological heterogeneity, which may provide a foundation for mechanistic studies and personalized treatment.

Objective Behçet syndrome (BS) is a systemic autoimmune vasculitis characterized by immune dysregulation involving multiple immune cell subsets. CD161+ Treg cells exhibit proinflammatory properties and impair immune regulation during inflammation. This study aimed to investigate the alterations in CD161+ Treg cells in BS and their clinical relevance, particularly in disease pathogenesis and neurologic involvement. Methods This prospective multicenter study included 182 patients diagnosed with BS at the three hospitals between 2018 and 2024, 166 patients with systemic lupus erythematosus (SLE) and 149 patients with rheumatoid arthritis (RA) and 114 patients with healthy controls (HCs). Demographic and clinical data were recorded. CD4+CD25highCD127lowCD161+ T cells (CD161+ Treg cells) in peripheral blood were analyzed via flow cytometry. Statistical analysis included the Wilcoxon rank‐sum test, Fisher's exact test, and logistic regression, with P < 0.05 considered significant. Results Patients with BS had a significantly higher proportion among total Treg cells and CD4+ T cells, as well as higher absolute number of CD161+ Treg cells compared to HCs. CD161+ Treg cell levels negatively correlated with Foxp3+ Treg cells and positively correlated with Teff cells. Patients with BS had higher absolute number of CD161+ Treg cells than that in patients with SLE and in patients with RA. Moreover, patients with BS with higher erythrocyte sedimentation rate or C‐reactive protein or with neurologic involvement exhibited higher CD161+ Treg cells, which were identified as a risk factor for neurologic involvement. Among 41 patients with BS observed after treatment, CD161+ Treg cells significantly decreased, correlating with reduced disease activity. Conclusion Patients with BS exhibit an increased CD161+ Treg cells in peripheral blood, which may contribute to immune dysregulation and neurologic involvement. The reduction of CD161+ Treg cells following treatment suggests their potential role as a biomarker for disease activity in BS.

ABSTRACT Fabrication of cross‐scaled ultrasensitive surface‐enhanced Raman scattering (SERS) substrates ranging from nanogaps for efficient localized surface plasmon resonances (LSPRs) to mm2‐size for easy operation is challenging. Here, we propose femtosecond‐laser‐induced periodic phase‐transition (fs‐LIPPT) of 1T’‐MoTe2 nanograting template, inducing Au nanostructures for frequency‐shift digital‐SERS immunoassay. The interference between the incident transverse electric wave and propagation wave in the 2H‐MoTe2/SiO2‐interlayer waveguide triggers the highly homogeneous periodic 1T’ phase‐transition pattern. The Au nanoparticles (AuNPs) are subsequently reduced at the 1T’ regions in chloroauric acid solution, forming a subwavelength AuNPs@1T’‐MoTe2 nanograting with 295.0 ± 8.1 nm in period. The Fano resonances by coupling the narrow‐band guided‐mode resonances supported in the 1T’‐MoTe2/SiO2‐interlayer nanograting with the broadband LSPRs in AuNPs promote optical localization, achieving the superior performance with a limit of detection in 10−14 m and a SERS performance factor of 7.5 × 106 for rhodamine 6G (R6G). A paradigm of frequency‐shift digital‐SERS immunoassay for serological diagnosis is established using the R6G‐labeled AuNPs@1T’‐MoTe2 nanograting conjugated with immunoglobulin G of rheumatoid arthritis, by which the discrimination accuracy is unexpectedly close to unity. The present work provides a novel protocol for SERS serum immunoassay, opening opportunities for early diagnosis and accurate prognosis of autoimmune diseases by blood test in the future.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by persistent synovitis. The synovial inflammation observed in RA exhibits significant heterogeneity among patients. To examine the relationship between major immune cell infiltration profiles in synovium and both local synovitis and systemic manifestations of RA. This cross-sectional study enrolled 22 RA patients (mean disease duration: 7.1 years). Synovial biopsies were assessed using the Krenn synovitis scoring system (no/low/high-grade) and immunohistochemical pathotyping (lympho-myeloid, diffuse-myeloid, pauci-immune). Clinical parameters, including the Disease Activity Score-28 (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and autoantibody status, were systematically analyzed. Immunohistochemical analysis identified three distinct synovial pathotypes, characterized by specific distributions of CD3⁺ T cells, CD68⁺ macrophages, CD20⁺ B cells, and CD138⁺ plasma cells. Synovitis severity, classified using the Krenn scoring system, demonstrated significant differences in synovial inflammation and stromal hyperplasia. High-grade synovitis exhibited significantly increased infiltration of CD20⁺ B cells (p = 0.025) and CD138⁺ plasma cells (p = 0.034) compared to non-inflamed tissues. Pathotype distribution analysis revealed a predominance of the pauci-immune subtype in the no-synovitis group (59.1

To investigate the dose effect of methylprednisolone (MP) on peripheral lymphocyte profiles in patients with systemic lupus erythematosus (SLE). This study investigated the impact of varied MP doses on peripheral lymphocyte subtypes in SLE patients. We conducted a prospective study involving 51 SLE patients, categorized into four groups (40 mg/day, 80 mg/day, 500 mg/day, and 1000 mg/day) based on the administered MP dosage during hospitalization. We analyzed the lymphocyte count and proportion in peripheral blood, along with their subpopulations, before and after MP treatment using the paired Mann–Whitney U test. Treatment with a clinically rational dose of MP (40 mg/day or 80 mg/day) resulted in increased lymphocyte counts, encompassing total lymphocytes, T cells, CD4 + T cells, regulatory T cells (Treg), and effector T cells (Teff) in the short term. Conversely, the counts of these cells decreased with pulse MP (500 mg/day or 1000 mg/day). The percentage of Treg cells and the Treg/Teff ratio increased following 40 mg or 80 mg MP/day treatment, whereas they decreased after pulse therapy. A gradual augmentation in the count and percentage of Treg cells was observed during continuous administration of 40 mg or 80 mg MP/day for 1 week, while in patients receiving pulse therapy, Treg cells tended to decrease during the therapy but rapidly recovered upon MP reduction. Lower doses of MP in the short term increased Treg cells, inhibiting systemic inflammation in SLE. High-dose pulse therapy exhibited a suppressive effect on Tregs.

Low-dose interleukin 2 (IL-2) administration has been shown to selectively modulate regulatory T (Treg) cell abundance and alleviate the progression of systemic lupus erythematosus (SLE). IL-2 level could be indicator of low-dose IL-2 usage in SLE patients. However, current methods for IL-2 detection are generally not sensitive to be used in clinic. This study aims to establish flow cytometry-based IL-2 detection as a feasible approach in determining IL-2 in peripheral blood of SLE patients. Flow cytometry was used to quantify the relative mean fluorescence intensity (MFI) of IL-2 in CD3+T cells and other lymphocyte subsets in peripheral blood mononuclear cell (PBMCs) from a cohort of 134 SLE patients and 112 healthy controls (HC). Correlations between IL-2 MFI and clinical or laboratory parameters in SLE patients were also investigated. MFI of IL-2 represented IL-2 expression in CD3+T cells. IL-2 MFI was significantly lower in SLE patients compared to the HC group and negatively associated with anti-ribosomal protein antibodies, erythrocyte sedimentation rate (ESR), and blood urea. Conversely, it was positively correlated with IgA and hemoglobin. These associations with IgA, hemoglobin, ESR, and blood urea remained significant after adjusting for age and disease duration. IL-2 level was also positively correlated with the relative abundance of Th1, Th2, and Th17 cells. Furthermore, MFI of IL-2 recovered with effective treatment in SLE patients. MFI of IL-2 serves as a feasible marker of IL-2, which is significantly decreased in SLE patients and recovered with treatment, suggesting its potential for assessing short-term disease status and treatment response in SLE patients.

BACKGROUND:Macrophages play a crucial role in SLE associated diffuse alveolar hemorrhage (DAH), and Axl receptor tyrosine kinase (AxlTK) is prominently expressed in macrophages. This study aimed to evaluate the role of AxlTK in the onset of lupus-associated DAH. METHODS:The expression of soluble Axl (sAxl) in serum from SLE patients with/without DAH was detected by ELISA. Wild-type (WT) and AxlTK-Knockout (Axl-KO) mice were used to explore the role of AxlTK in the development of DAH in a pristane-induced lupus model, and the therapeutic effect of AxlTK inhibitor TP-0903 was also assessed. The effect of AxlTK on macrophage function was demonstrated by flow cytometry and ELISA. The macrophages from the lung tissues of WT and Axl-KO DAH mice were collected for RNA-sequencing to further explore the mechanism. RESULTS:The serum sAxl level was higher in SLE patients with DAH, and correlated with disease activity. And AxlTK was highly expressed on macrophages from the lungs of DAH mice. Compared with WT mice, both Axl-KO mice and TP-0903-treated mice exhibited less severe DAH, with reduced iNOS+F4/80+ macrophages and elevated CD206+F4/80+ macrophages in lung tissues. Further experiments revealed that AxlTK deficiency inhibited the polarization of bone marrow-derived macrophages (BMDMs) and decreased the uptake of apoptotic cells. Additionally, RNA-sequencing analysis revealed that AxlTK may affect macrophage activation in DAH mice through inflammatory pathways. CONCLUSION:AxlTK is involved in the development of DAH by regulating the activation of macrophages and might be a potential therapeutic target for SLE with DAH.

Rheumatoid arthritis (RA) is a serious chronic systemic autoimmune disease leading to joint destruction for progressive disability. Accurate non-invasive diagnosis of RA in the early stages is vital to timely precision treatment. The advancements of surface-enhanced Raman spectroscopy (SERS) in label-free liquid biopsy for noninvasive diagnosis have been witnessed in the past decade. The recently-developed digital SERS (dSERS) further overcomes the spectral intensity fluctuation, strengthening reliability and robustness for quantitative analysis. Here we propose a high-throughput dSERS substrate by fs-laser parallel fabrication utilizing microsphere-generated photonic nanojet (PNJ), by which the nanohole-in-microsphere array (NiMA) is obtained with the minimum diameter of 115 nm and depth of 600 nm. The Au-nanoparticle-coated NiMA possesses high precision in liquid sampling (10-18 L) and ultralow limit of detection. The discrete nanohole distribution with high homogeneity guarantees the independent acquisition of Raman spectrum for accuracy of Poisson's statistics in a small spectral dataset volume. The NiMA substrate is employed to collect the sera and diagnose by quantitative recognition of three biomarkers (homocitrulline, L-tryptophan and L-citrulline) in sera by dSERS approach. The accuracy of 88.0 %, sensitivity of 92.9 % and specificity of 81.8 % in distinguishing RA patients manifests the feasibility of serum dSERS protocol for clinical early-stage diagnosis.

Alterations in intestinal microbiota have been identified as a key risk factor in rheumatoid arthritis (RA). This study presents a multidimensional gut microbiota profile from a large cohort of RA patients, stratified by disease stage and treatment regimens, and compared to healthy controls. Our dataset comprises gut microbiota profiles from 2,238 individuals, including 1,034 RA patients (Ascia Pacific RA cohort, APRAC) and 1,204 healthy controls. This dataset is enriched with detailed clinical metadata, including patient profiles, treatment histories, and environmental factors, providing a comprehensive “disease exposome” for RA. By integrating 16S rRNA gene sequencing with demographic, clinical, and environmental data, we offer a valuable resource to explore the complex relationships between gut microbiota and RA progression. This large-scale dataset is expected to be a foundation for collaborative research, advancing our understanding of the microbiome’s systemic effects in RA and other autoimmune diseases and potentially guiding new therapeutic approaches.

The function of transient receptor potential vanilloid (TRPV) cation channels governing B cell activation remains to be explored. We present evidence that TRPV2 is highly expressed in B cells and plays a crucial role in the formation of the B cell immunological synapse and B cell activation. Physiologically, TRPV2 expression level is positively correlated to influenza-specific antibody production and is low in newborns and seniors. Pathologically, a positive correlation is established between TRPV2 expression and the clinical manifestations of systemic lupus erythematosus (SLE) in adult and child SLE patients. Correspondingly, mice with deficient TRPV2 in B cells display impaired antibody responses following immunization. Mechanistically, the pore and N-terminal domains of TRPV2 are crucial for gating cation permeation and executing mechanosensation in B cells upon antigen stimulation. These processes synergistically contribute to membrane potential depolarization and cytoskeleton remodeling within the B cell immunological synapse, fostering efficient B cell activation. Thus, TRPV2 is critical in augmenting B cell activation and function.

Monocarboxylate transporter 1 (MCT1) exhibits essential roles in cellular metabolism and energy supply. Although MCT1 is highly expressed in activated B cells, it is not clear how MCT1-governed monocarboxylates transportation is functionally coupled to antibody production during the glucose metabolism. Here, we report that B cell-lineage deficiency of MCT1 significantly influences the class-switch recombination (CSR), rendering impaired IgG antibody responses in Mct1 f/f Mb1 Cre mice after immunization. Metabolic flux reveals that glucose metabolism is significantly reprogrammed from glycolysis to oxidative phosphorylation in Mct1 -deficient B cells upon activation. Consistently, activation-induced cytidine deaminase (AID), is severely suppressed in Mct1 -deficient B cells due to the decreased level of pyruvate metabolite. Mechanistically, MCT1 is required to maintain the optimal concentration of pyruvate to secure the sufficient acetylation of H3K27 for the elevated transcription of AID in activated B cells. Clinically, we found that MCT1 expression levels are significantly upregulated in systemic lupus erythematosus patients, and Mct1 deficiency can alleviate the symptoms of bm12-induced murine lupus model. Collectively, these results demonstrate that MCT1-mediated pyruvate metabolism is required for IgG antibody CSR through an epigenetic dependent AID transcription, revealing MCT1 as a potential target for vaccine development and SLE disease treatment.

It is unknown if dysbiosis of microbiota plays a role in the initiation and severity of rheumatoid arthritis (RA). In a comprehensive study of 2297 individuals, including 1,064 RA patients and 1,233 healthy controls, we uncovered an age-related trajectory fluctuation of intestinal microbiota in RA which clearly coincided with the peak age of RA onset. Patients at RA onset exhibited a significant reduction in anti-inflammatory species like Akkermansia muciniphila , Butyrivibrio proteoclasticus , and Rumlnococcus albus . Conversely, pro-inflammatory bacteria Escherchia coli, Parabacteroldes distesonis , and Velllonella parvula were largely enriched. Samples in different clusters show distinct microbial patterns, and associated with treatment response. Specific gut microbiota was closely linked to RA's clinical features and systemic involvements, especially interstitial lung disease (ILD). Our predictive model based on gut microbiota successfully distinguished RA with systemic impairment from those with mainly joint involvements. Additionally, a 6-year follow-up cohort showed that lower disease activity associated with increased abundance of Streptococcu salivarius, Anaerostipehadrus , and lactobacillus fermentum . These findings suggest that gut microbiota may trigger RA initiation, and are associated with aggravated and systemic damages of the disease, and could lead to more personalized and effective treatment strategies.

Behcet's syndrome (BS) is a vasculitis characterized by immune dysregulation. Biomarkers are valuable for assessing clinically atypical pathogenesis. We aimed to investigate the distribution of different biomarkers and their effects on the clinical features of patients with BS in a large-scale, real-world study. This is a retrospective, single-center study. In total, 502 patients diagnosed with BS were enrolled in this study. We analyzed the clinical features of this cohort and divided patients’ symptoms into six categories, including mucocutaneous, articular, neurological, gastrointestinal, vascular, and ocular involvements. HLA-B51 cells, autoantibodies, and subsets of immune cells from the patients were tested. Pearson’s correlation, Wilcoxon rank sum test and multivariate logistic regression were used for data analysis. Various autoantibodies were detected in the serum of 40.8