Arthritis Research & Therapy最新文献

{"title":"Vagotomy and the incidence of rheumatoid arthritis and osteoarthritis: a Danish register-based study","authors":"Matthew C. Baker, Dávid Nagy, Suzanne Tamang, Erzsébet Horváth-Puhó, Henrik Toft Sørensen","doi":"10.1186/s13075-025-03567-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03567-y","url":null,"abstract":"Given the potential role of vagus nerve stimulation in treating rheumatoid arthritis (RA), we examined the incidence of RA and osteoarthritis (OA) in patients who underwent different forms of vagotomy that disparately affect the inflammatory reflex. Using nationwide health registries, we constructed cohorts of patients in Denmark who underwent truncal or superselective vagotomy between 1977 and 1995 and comparison members from the general population matched 10:1 on birth year, sex, and calendar year. We identified incident RA or OA and used Cox proportional hazards models to compute adjusted hazard ratios (aHRs) and corresponding 95% CI. Our cohorts consisted of 2,260 truncal vagotomy patients matched with 22,610 comparators, and 3,810 superselective vagotomy patients matched with 38,090 comparators. The incidence rate (IR) of RA per 1,000 person-years (95% CI) in the truncal vagotomy cohort was 10.2 (6.5–15.3) versus 7.2 (6.1–8.4) in the matched comparison cohort. The aHR (95% CI) for RA development was 2.62 (1.47–4.67) in the truncal vagotomy cohort and 1.05 (0.51–2.17) in the superselective vagotomy cohort, with respect to comparison cohorts. The risk of developing OA was not significantly different for either vagotomy cohort compared with comparison cohorts. Truncal vagotomy was associated with an increased incidence of RA; this association was not observed with superselective vagotomy. No association with either form of vagotomy was seen with OA. These findings support the hypothesis that disruption of vagus nerve signaling impacts the inflammatory reflex and contributes to the development of RA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"5 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atf3 + senescent chondrocytes mediate meniscus degeneration in aging","authors":"Jing-Yi Wang, Yao-Hui Liu, Xiao Wang, Min Ma, Zhang-Yi Pan, Ao-Yuan Fan, Lai-Ya Lu, Zheng Liu, Kun Tao, Feng Yin","doi":"10.1186/s13075-025-03566-z","DOIUrl":"https://doi.org/10.1186/s13075-025-03566-z","url":null,"abstract":"Meniscus degeneration contributes to knee arthritis progression, but the cellular and molecular mechanisms of meniscus aging remain poorly understood. We aimed to characterize age-related changes in the rat meniscus using single-cell RNA sequencing (scRNA-seq) and identify key pathogenic cell populations and pathways. Meniscal tissues from young (12 weeks) and aged (24 months) rats were processed for histology, flow cytometry, and scRNA-seq. Bioinformatics tools, including Seurat, Monocle 2, and CellChat, were used to analyze cellular composition, pseudotime trajectories, and intercellular communication. Senescence-related features and signaling pathways were evaluated. Knee joint of aged rats exhibited higher Osteoarthritis Research Society International (OARSI) scores and synovial inflammation. scRNA-seq revealed three major chondrocyte subpopulations: Sox9 + stable chondrocytes, Fndc1 + fibrochondrocytes, and Atf3 + senescent chondrocytes. Aging caused a significant increase in Atf3 + senescent chondrocytes, characterized by the expression of senescence markers (Cdkn1a/Cdkn2a) and activation of inflammatory pathways such as tumor necrosis factor (TNF) and nuclear factor-κB (NF-κB). These cells were predominantly located at the endpoint of differentiation trajectories. CellChat analysis identified the ANGPTL4-SDC4 axis as a key signaling pathway mediated by Atf3 + cells. Immunostaining confirmed elevated Angiopoietin-Like Protein 4 (ANGPTL4) expression in aged menisci. We identified Atf3 + senescent chondrocytes as a key pathogenic population in the aging meniscus, driving degeneration via the ANGPTL4 pathway. Targeting Atf3 + cells or ANGPTL4 signaling may offer new therapeutic strategies for age-related meniscus degeneration and arthritis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"114 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondrocyte lysates activate NLRP3 inflammasome-induced pyroptosis in synovial fibroblasts to exacerbate knee synovitis by downregulating caveolin-1","authors":"Xue Du, Ruonan Liu, Zongrui Jiang, Chengyun Zhang, Zhijian Yang, Shu Hu, Zhiqi Zhang","doi":"10.1186/s13075-025-03573-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03573-0","url":null,"abstract":"Synovitis, among the most common signs of early-stage osteoarthritis (OA), is mainly mediated by fibroblast-like synoviocytes (FLSs). Cartilage destruction creates chondrocyte lysates (CLs) that activate synovial inflammation. A comprehensive understanding of chondrocyte–FLS communication might offer novel, specific therapeutic targets for treating synovitis and OA. Hence, we sought to uncover the specific role of CLs in OA-FLSs and synovitis. Isolated CLs were cocultured with FLSs to test whether they could stimulate synovial inflammation. A model of medial meniscus destabilization was prepared in C57BL/6 mice and NLRP3 knockout mice, and adeno-associated virus overexpressing Caveolin-1 (CAV1) was intra-articularly injected for 8 weeks once a week after dissection of the medial meniscus (DMM). Proteins expressed in FLSs with and without CL coculture were screened using liquid chromatography-tandem mass spectrometry to identify CL-specific regulators of NLRP3 inflammasome-mediated pyroptosis. CLs were engulfed by FLSs, which aggravated inflammatory cytokine release and NLRP3 inflammasome-mediated FLS pyroptosis. NLRP3 expression was significantly upregulated in human OA-FLSs and FLSs cocultured with CLs, while CAV1 was downregulated. CAV1 overexpression reversed the inflammatory phenotype in FLSs and simultaneously rescued pyroptosis in CL-pre-treated FLSs. Both synovial hyperplasia and inflammatory infiltration in C57BL/6 mice with DMM surgery were alleviated after intra-articular AAV-CAV1 injection. Moreover, the CL-specific protein LIM-containing lipoma preferred partner (LPP) markedly exacerbated FLS pyroptosis and inflammation. CLs were endocytosed by FLSs through CAV1, and the CL-specific protein LPP stimulated NLRP3 inflammasome-mediated pyroptosis and synovitis by inhibiting CAV1 expression. Our findings offer a novel therapeutic target for treating synovitis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"14 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender differences in clinical and prescribing characteristics of biologic and targeted synthetic drugs in naïve patients with rheumatoid arthritis: Data from BIOBADASER III registry","authors":"Paloma Vela-Casasempere, Lucía Otero-Varela, Silvia Gómez Sabater, Rocío Caño Alameda, Cristina Campos Fernández, Jerusalén Calvo-Gutiérrez, Yanira Pérez-Vera, Sara Manrique Arija, Sagrario Bustabad, Javier Manero Ruiz, María Dolores Ruiz Montesino, Lucía Ruíz Gutiérrez, Antonio Mera Varela, Manuel José Moreno Ramos, Fernando Sánchez-Alonso, Isabel Castrejón","doi":"10.1186/s13075-025-03571-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03571-2","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that can lead to progressive joint damage and irreversible disability when inadequately treated. RA is more common in women than in men. Disease characteristics differ between genders in terms of comorbidities, extra-articular manifestations, quality of life, disease activity and functional scores. There is a possibility that RA may be managed differently depending on gender: under-treated due to professional bias when prescribing advanced therapies, or over-treated due to overestimation of disease activity. Our primary objective was therefore to examine gender differences in the time course from RA diagnosis to initiation of the first biologic disease-modifying antirheumatic drug (bDMARD) or targeted synthetic DMARD (tsDMARD) and to identify factors associated with earlier or later prescribing. We also aimed to assess the differences between men and women in clinical characteristics and disease activity at initiation of the first b/tsDMARD among bio-naïve RA patients. We analyzed RA patients from the BIOBADASER III registry who began their first b/tsDMARD between 2000 and 2023, stratified by treatment start year. Clinical characteristics were compared by sex, using linear regression models for DAS28. Kaplan–Meier curves and multivariate Cox regression identified factors influencing treatment initiation timelines. We included 3,384 patients (78.1% women). Males presented higher cardiovascular risk, females more osteoporosis and Sjögren Syndrome. At treatment start, females had lower mean age (54.8 vs. 57 years, p < 0.001) but longer disease duration (7.3 vs. 6.7 years, p = 0.031); higher DAS28-ESR, but not DAS28-CRP; higher subjective components of DAS28 and ESR but lower CRP and no differences in objective components. Disease duration differed between sexes only in the most recent cohort (≥ 2017, HR 0.9 (95% CI 0.81; 0.99), p = 0.026): female sex, age, and treatment with csDMARDs (other than methotrexate) were associated with later prescribing, whereas tobacco, obesity and treatment with methotrexate or glucocorticoids with earlier. Later prescribing in women despite higher activity rates merits reflection. Discrepancies between subjective and objective measures of DAS, and ESR and CRP, may reflect the need to establish different cut-off points for men and women, and opens a field of research worth exploring.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"52 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T cell therapy for juvenile-onset autoimmune diseases: a promising future?","authors":"Maurine Jouret, Sebastien Viel, Benjamin Fournier, Sarah Benezech, Jérome Avouac, Marc Scherlinger, Alexandre Belot","doi":"10.1186/s13075-025-03564-1","DOIUrl":"https://doi.org/10.1186/s13075-025-03564-1","url":null,"abstract":"Chimeric antigen receptor (CAR) T-cell therapy targeting B cells has shown promising results, including drug-free remission, in adult-onset autoimmune diseases. Extending this therapeutic approach to the pediatric population, particularly for juvenile autoimmune diseases, presents an exciting opportunity. However, challenges specific to juvenile-onset autoimmune conditions, such as long-term adverse events, heightened disease activity, and the imperative to reduce steroid exposure, must be considered. While this strategy appears viable for these severe conditions, the limited data available for this population and the absence of evidence on cases with a high genetic component, such as monogenic lupus, represent significant challenges. Most monogenic lupus cases are associated with innate immune defects, and the involvement of B cells in these genetic anomalies remains poorly understood. In this review, we examine the potential indications, current knowledge, and limitations of CAR-T cell therapy in juvenile-onset autoimmune diseases, extending the discussion beyond early-onset lupus.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking as a risk factor for rheumatoid arthritis: predominant association with IgA autoantibodies – comprehensive analysis of anti-modified protein antibodies with smoking and genetic risk factors in rheumatoid arthritis","authors":"Tineke J. van Wesemael, Fraser R. Morton, Judith W. Heutz, Marc P. Maurits, Annemarie L. Dorjée, Duncan Porter, Tom W. J. Huizinga, Karim Raza, Rene E. M. Toes, Rachel Knevel, Pascal H. P. de Jong, Anna Svärd, Diane van der Woude","doi":"10.1186/s13075-025-03543-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03543-6","url":null,"abstract":"Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of autoantibodies against modified proteins, known as anti-modified protein autoantibodies (AMPAs). While the relationship between different AMPA isotypes and various risk factors remains poorly understood, investigating this association is important for a deeper understanding of RA pathophysiology. Smoking, has its primary effects in the lungs, and it remains unclear whether smoking is preferentially linked to specific AMPA isotypes, such as IgA, which could suggest a mucosal origin. Therefore, we set out to investigate the association between smoking, genetic risk factors for RA, and the presence of specific AMPA isotypes, particular IgA. In 618 RA patients, anti-citrullinated protein antibodies (ACPA-) and anti-acetylated protein antibodies (AAPA-) IgA, -IgG and -IgM and RF-IgA and -IgM were measured by ELISA. Associations with genetic risk factors, smoking and autoantibodies were assessed with logistic regression analysis. For replication, a comprehensive meta-analysis incorporating 3309 RA patients was performed. Smoking was primarily associated with IgA AMPA, with associations that prevailed after correcting for the concurrent presence of AMPA IgG (ACPA-IgA OR 1.89 [1.14–3.12], AAPA-IgA 2.30 [1.35–3.94]). To further substantiate these results, we performed a meta-analysis of 3309 RA patients and observed that smoking was again predominantly associated with the combined presence of ACPA-IgA in addition to ACPA-IgG (OR 2.05 [1.69–2.49], p < 0.001) versus the single presence of ACPA-IgG (OR 1.18 [0.97–1.44], p = 0.11). A gene-environment interaction between the most important genetic risk factor for RA (the HLA shared epitope alleles) and smoking was only seen in patients that were both ACPA-IgG and ACPA-IgA positive, but not in patients who were only positive for ACPA-IgG. These data provide a pivotal refinement of existing knowledge regarding risk factor associations for RA and lend novel support to the hypothesis that smoking may exert its effect on RA by the induction of local (auto)immune responses at mucosal sites.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"48 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in omics and the integration of multi-omics in osteoarthritis research","authors":"Ye Liu, Vladimir Molchanov, David Brass, Tao Yang","doi":"10.1186/s13075-025-03563-2","DOIUrl":"https://doi.org/10.1186/s13075-025-03563-2","url":null,"abstract":"Osteoarthritis (OA) is a complex disorder driven by the combination of environmental and genetic factors. Given its high global prevalence and heterogeneity, developing effective and personalized treatment methods is crucial. This requires identifying new disease mechanisms, drug targets, and biomarkers. Various omics approaches have been applied to identify OA-related genes, pathways, and biomarkers, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics. These omics studies have generated vast datasets that are shaping the field of OA research. The emergence of high-resolution methodologies, such as single-cell and spatial omics techniques, further enhances our ability to dissect molecular complexities within the OA microenvironment. By integrating these multi-layered datasets, researchers can uncover central signaling hubs and disease mechanisms, ultimately facilitating the development of targeted therapies and precision medicine approaches for OA treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"48 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistin upregulates fatty acid oxidation in synoviocytes of metabolic syndrome-associated knee osteoarthritis via CAP1/PKA/CREB to promote inflammation and catabolism","authors":"Lu Ding, Jin-Yi Ren, Yi-Fan Huang, Jian-Zeng Zhang, Zi-Ran Bai, Yi Leng, Jun-Wei Tian, Jing Wei, Min-Li Jin, Guan Wang, Xia Li, Xin Qi","doi":"10.1186/s13075-025-03527-6","DOIUrl":"https://doi.org/10.1186/s13075-025-03527-6","url":null,"abstract":"Metabolic Syndrome (MetS), as a syndrome characterized by low-grade inflammation and energy metabolism disorders, is considered to be an important systemic risk factor for knee osteoarthritis (KOA). Our previous study showed that the protein level of serum resistin was positively correlated with the degree of metabolic disorder in MetS-OA. However, whether Resistin promotes the progression of KOA synovitis and the underlying mechanisms remain unclear. This study mainly investigateswhether there were metabolism disorder which promote inflammatory and catabolic phenotype in fibroblast-like synoviocytes (FLS) from KOA patients with MetS (MetS-KOA-FLS), and the roles and mechanisim of resistin in MetS-KOA-FLS. Comparative analysis of synovium and FLS from MetS-associated KOA (MetS-KOA) and non-MetS-associated KOA (nMetS-KOA) of females to detect the differences in inflammation, catabolism and glycolipid metabolism. Serum from MetS-KOA stimulated nMetS-KOA-FLS to detect the effect of MetS microenvironment on inflammation, catabolism and glycolipid metabolism of nMetS-KOA-FLS. Resistin stimulated MetS-KOA-FLS to explore the effect of resistin on inflammation and catabolism of MetS-KOA-FLS and its specific mechanism. Compared with nMetS-KOA-FLS, MetS-KOA-FLS expressed higher inflammatory related factors, catabolic enzymes, and showed stronger adhesive and invasive ability. Resistin was found to be an important factor in the serum and internal environment of MetS-KOA patients, and it mediated the differences in fatty acid oxidation (FAO) between the two groups. Resistin activated the PKA/CREB pathway through CAP1 and upregulated FAO, promoting the inflammatory and catabolic phenotype of MetS-KOA-FLS. This study clarifies the mechanism by which MetS causes synovitis from a metabolic perspective and provides new ideas for further research and treatment of MetS-KOA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"8 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive comparative analysis of infrapatellar fat pad morphologies in a longitudinal knee osteoarthritis exploratory study: new insights into its role as an independent prognostic marker","authors":"Jean-Pierre Pelletier, Patrice Paiement, François Abram, Marc Dorais, Jean-Pierre Raynauld, Johanne Martel-Pelletier","doi":"10.1186/s13075-025-03513-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03513-y","url":null,"abstract":"No established markers can effectively phenotype knee osteoarthritis (OA) patients into subgroups. Infrapatellar fat pad (IPFP) morphology data that can forecast disease symptoms, structural changes, and knee replacement (KR) are sparse and conflicting. This 96-month longitudinal exploratory study aimed to identify which IPFP morphological features were the most effective independent prognostic markers against these outcomes. This longitudinal study analyzed 1075 target knees (one knee per participant) from the Osteoarthritis Initiative (OAI) progression cohort. Structural changes include cartilage, bone marrow lesions (BMLs), and joint effusion volumes assessed using automated and quantitative magnetic resonance imaging systems (MRI). The IPFP global and signal (hyper- and hypo-) intensity volumes and areas were assessed using MRI combined with a newly developed, fully automated neuron-driven technology. Symptoms were evaluated using WOMAC scores. Data on KR was obtained from the OAI database. Data were collected at baseline and 12, 24, 48 and 96 months and analyzed using a mixed model for repeated measures (MMRM) or ANCOVA. The baseline characteristics were mild to moderate knee OA. Over time, disease symptoms (WOMAC), cartilage volume, IPFP global and hypointense signal volumes, and maximal and hypointense signal areas decreased (all p≤0.001). Joint effusion and hyperintense signal volume and area increased (both p≤0.001). Associations were found between IPFP morphologies at inclusion and changes in cartilage volume (hypointense and hyperintense volumes, 48, 96 months, p≤0.04), BML volume (global volume 48 months, p=0.05; hyperintense area, 12 months, p≤0.04), and effusion volume (hypointense volume 48 months and hyperintense volume 96 months, p≤0.05). At inclusion, smaller IPFP sizes (below median) were associated with cumulative KR at 96 months (global and hypointense volumes, p≤0.04 and maximum area, p=0.05). This longitudinal exploratory study, leveraging a fully automated technology, highlights that i) IPFP volume (global and both signals) is superior to area metrics in predicting long-term structural changes in OA, and ii) smaller IPFP volume and area are linked with reduced need for KR. These findings provide new insights into the usefulness of IPFP morphology as a predictive biomarker of knee OA outcomes, offering a new approach to stratifying knee OA patients.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"6 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatic analysis and experimental verification reveal expansion of monocyte subsets with an interferon signature in systemic lupus erythematosus patients","authors":"Jimin Zhang, Wuwei Zhuang, Yan Li, Chaoqiong Deng, Jingxiu Xuan, Yuechi Sun, Yan He","doi":"10.1186/s13075-025-03560-5","DOIUrl":"https://doi.org/10.1186/s13075-025-03560-5","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by chronic inflammation and multi-organ damage. A central factor in SLE pathogenesis is the excessive production of type I interferon (IFN-I), which drives immune dysregulation. Monocytes, key components of the immune system, significantly contribute to IFN-I production. However, their specific roles in SLE remain incompletely understood. This study utilized bioinformatics and statistical analyses, including robust rank aggregation (RRA), DESeq2, and limma, to analyze transcriptome data from peripheral blood mononuclear cells (PBMCs) and monocytes of SLE patients and healthy controls. Single-cell RNA sequencing (scRNA-seq) data were processed using the Seurat R package to identify and characterize monocyte subsets with a strong IFN-driven gene signature. Flow cytometry was employed to validate key findings, using markers such as CD14, SIGLEC1, and IRF7 to confirm monocyte subset composition. Our research has found that monocytes in SLE undergo IFN-driven transcriptional reprogramming, with the upregulation of key interferon signature genes (ISGs), forming the SLE-Related Monocyte Signature (SLERRAsignature). Moreover, the composition of mononuclear phagocyte subsets in SLE patients changes, with an increase trend in the proportion of the CD14Mono8 subset in the flare group. The differentially expressed genes (DEGs) in 13 mononuclear phagocyte subsets of SLE are mainly ISGs, and the expression of ISGs is higher in severe patients. We identified SIGLEC1+IRF7+ monocytes among these subsets and for the first time discovered this group of cells in the peripheral blood of healthy individuals. In SLE, the enrichment score of the gene set representing SIGLEC1+IRF7+ monocytes is positively correlated with the severity of SLE. Finally, flow cytometry confirmed that the frequency of CD14+SIGLEC1+IRF7+ monocytes in PBMCs was higher in SLE compared with healthy controls. Our study found that the expansion of IFN-I-producing monocyte subsets, particularly the CD14+SIGLEC1+IRF7+ subset, plays a crucial role in SLE pathogenesis. This subset may serve as a potential biomarker and therapeutic target for managing SLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"17 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}