Arthritis Research & Therapy最新文献

{"title":"Artemisinin increases susceptibility to ferroptosis of fibroblast-like synoviocytes in rheumatoid arthritis.","authors":"Maoyuan Li, Jiahao Wang, Yunyuan Yu, Liangliang Wang, Feng Lu, Shishuo Li, Jiale Wang, Yimin Liu, Guangrong Yin, Chao Xu, Yuji Wang","doi":"10.1186/s13075-026-03853-3","DOIUrl":"10.1186/s13075-026-03853-3","url":null,"abstract":"<p><strong>Objective: </strong>Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by extensive synovial hyperplasia. Artemisinin (ART), a compound extracted from the traditional Chinese herb artemisia annua, has been proven to have anti-malarial and anti-cancer effects. Recently, the ability of artemisinin to induce ferroptosis has shown inhibitory effects on tumor cell proliferation. This study intends to examine whether artemisinin can inhibit the proliferation of RA synovial cells by sensitizing them to ferroptosis.</p><p><strong>Method: </strong>The effect of artemisinin on fibroblast-like synoviocytes (FLSs) were detected by methods such as CCK8, Western Blot, and immunofluorescence. A collagen-induced mouse model of rheumatoid arthritis was established by injecting collagen and Freund's adjuvant, and the mice were treated with artemisinin following model induction. Synovium was extracted, and imaging examinations along with immunostaining were used to identify the progression of ferroptosis.</p><p><strong>Results: </strong>The results revealed that ART increases the susceptibility of FLSs to ferroptosis inducers. The expression of ferroptosis-related proteins, such as glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), was decreased compared with controls. Meanwhile, intracellular lipid peroxides continued to accumulate after artemisinin treatment. Additionally, ferroptosis inhibitors such as deferoxamine (DFO) and Ferrostatin (Fer-1) can inhibit artemisinin-sensitized ferroptosis. The artemisinin-sensitized ferroptosis was related to the increase of P53. In vivo experiments on collagen-induced arthritis mouse models further confirmed that artemisinin relieved joint injury by sensitizing synovial ferroptosis, which was abolished by ferroptosis inhibitors.</p><p><strong>Conclusion: </strong>Artemisinin can increase the sensitivity of FLSs to ferroptosis and inhibit the proliferation of synovial cells in rheumatoid arthritis. The P53-SLC7A11 pathway play the important role in this process.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tripartite motif containing 21 autoimmunity primes CD8⁺ cell-mediated lung inflammation: an in vivo model of interstitial lung disease pathogenesis.","authors":"Yulu Qiu, Qin Wu, Lu Liu, Wenjuan Zhao, Yue Wang, Fang Wang, Wenfeng Tan","doi":"10.1186/s13075-026-03850-6","DOIUrl":"10.1186/s13075-026-03850-6","url":null,"abstract":"<p><strong>Background: </strong>Anti-Ro52 [Tripartite Motif Containing 21 (TRIM21)] antibodies are strongly associated with interstitial lung disease (ILD) in connective tissue diseases (CTDs), yet the underlying mechanisms remain elusive. This study aimed to elucidate the mechanisms by which TRIM21 autoimmunity drives ILD using an in vivo model.</p><p><strong>Methods: </strong>A murine model of TRIM21 autoimmunity was established by immunizing mice with full-length recombinant TRIM21 protein. Lung immune infiltration and antibody production were assessed. To mimic viral triggers, mice received poly(I:C). Immune cell subsets and transcriptional changes were analyzed using flow cytometry, RNA sequencing, and immunohistochemistry.</p><p><strong>Results: </strong>TRIM21 immunization induced systemic autoantibody production and B cell activation, which were associated with selective pulmonary inflammation marked by IgG deposition. Upon poly(I:C) challenge, lung inflammation was markedly exacerbated, with increased infiltration of CD8⁺ cells and CD11b⁺ myeloid cells and enrichment of chemokine signaling pathways. RNA sequencing identified Ccl6 as a top upregulated gene, and its protein expression was spatially validated in inflamed lung tissue.</p><p><strong>Conclusion: </strong>These findings support a pathogenic role for anti-Ro52/TRIM21 autoimmunity in CTD-associated ILD. Our in vivo model reveals a lung-predominant inflammatory response associated with CD8⁺ cell that is amplified by viral mimicry and accompanied by CCL6 signaling, offering mechanistic insight and potential therapeutic targets in anti-Ro52 positive ILD.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148325762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting inflammatory and angiogenic responses by small-molecule kinase inhibitors in a 3D macrophage-containing spheroid model of rheumatoid arthritis synovial tissue.","authors":"Eva M L Philippon, Lisanne J E van Rooijen, Aldo Jongejan, Gary P Sims, Jeeho Lee, Lichchavi Rajasinghe, Jan Piet van Hamburg, Conny J van der Laken, Sander W Tas","doi":"10.1186/s13075-026-03849-z","DOIUrl":"10.1186/s13075-026-03849-z","url":null,"abstract":"<p><strong>Background: </strong>In rheumatoid arthritis (RA), interactions between macrophages, fibroblast-like synoviocytes (FLS), and endothelial cells (ECs) drive synovial tissue (ST) inflammation and pathological angiogenesis. Preclinical models reflecting this crosstalk are needed to evaluate novel therapies. We developed a human 3D model of RA ST to assess inflammatory mechanisms and responses to small-molecule kinase inhibitors.</p><p><strong>Methods: </strong>Polarized M1-like or M2-like macrophages were co-cultured with RAFLS and ECs to generate spheroids embedded in a collagen-based scaffold. Spheroids were unstimulated or exposed to pro-inflammatory stimuli, including tumor necrosis factor-α (TNF) or RA synovial fluid (SF). Treatment effects of tofacitinib (JAK1/3 inhibitor) and an IKKβ inhibitor (IKKβi; targeting NF-κB signaling) were evaluated. Readouts included spheroid outgrowth and macrophage distribution quantified by semi-automated image analysis (n = 8), cytokine production measured by ELISA/Luminex (n = 8), and RNA sequencing to identify differentially expressed genes (n = 4).</p><p><strong>Results: </strong>M1-like macrophages exhibited higher core retention, while M2-like macrophages showed increased outward migration (p < 0.05). M1 spheroids demonstrated elevated expression of M1 markers, chemokines, and EC-activating signatures, whereas M2 spheroids upregulated pathways related to matrix remodeling, migration, and immunoregulation (FDR < 0.05). In M1 spheroids, TNF and SF increased macrophage core density compared with unstimulated conditions (p < 0.01) and exhibited differential effects on spheroid outgrowth. SF induced RA-associated molecular programs that were broadly suppressed by IKKβi, whereas tofacitinib selectively reduced JAK-dependent signaling (FDR < 0.05). IKKβi significantly decreased TNF-induced mediators (IL-8: p < 0.001, M-CSF: p < 0.05, SPP1: p < 0.001), and tofacitinib primarily inhibited IL-6 production (p < 0.01).</p><p><strong>Conclusions: </strong>This human 3D multicellular in vitro spheroid model of synovial inflammation recapitulates key RA pathological processes and provides a robust platform for mechanistic studies and therapeutic evaluation.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of ABP-671 in healthy participants and patients with hyperuricemia and gout: a proof-of-concept study.","authors":"Jin Wang, Lan Zhang, Ullrich Schwertschlag, Jingfei Li, Yan Yang, Adam W Jin, Roy J Wu, Chaoying Hu, Dongfang Shi","doi":"10.1186/s13075-026-03840-8","DOIUrl":"10.1186/s13075-026-03840-8","url":null,"abstract":"<p><strong>Background: </strong>This proof-of-concept study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABP-671, a novel URAT1 inhibitor, in healthy participants and in patients with hyperuricemia and gout.</p><p><strong>Methods: </strong>This single-center, randomized, double-blind, placebo-controlled phase I/IIa clinical trial consisted of two parts: a single ascending dose study (SAD) in healthy participants (0.5, 1, 3, and 6 mg, with two participants receiving placebo and six participants receiving ABP-671 tablets per dose cohort), and a multiple ascending dose (MAD) study in patients with hyperuricemia and gout (1, 2, 4, 6 and 12 mg daily, with two patients receiving placebo and seven patients receiving ABP-671 tablets per cohort).</p><p><strong>Results: </strong>Thirty-two and 45 Chinese participants were enrolled in the SAD and MAD studies, respectively. In the SAD and MAD studies, eight (25.0%) and 24 (53.3%) participants reported treatment-emergent adverse events (TEAEs), respectively; there were no serious AEs (SAEs), and no grade ≥ 3 TEAEs. In the MAD study, the maximum mean serum urate decrease from baseline in patients with gout was 17.7% (placebo), 56.4% (1 mg QD), 58.1% (2 mg QD), 69.4% (4 mg QD), 77.0% (6 mg QD), and 79.2% (12 mg QD), respectively. The maximum mean serum urate decrease from baseline in serum urate in patients with hyperuricemia was 19.9% (placebo), 50.1% (1 mg QD), 64.1% (2 mg QD), 73.2% (4 mg QD), 81.2% (6 mg QD), and 82.1% (12 mg QD), respectively.</p><p><strong>Conclusions: </strong>ABP-671 had an acceptable safety profile in Chinese healthy participants and patients with hyperuricemia and gout. ABP-671 reduced serum urate levels in a dose-dependent manner.</p><p><strong>Trial registration: </strong>https://chinadrugtrials.org.cn (No. CTR20211668) .</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300702","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":"Osteoarthritis pain inversely correlates with histidine and glutamine following CSF and serum profiling.","authors":"Isobel K Dunstan, Line J H Rasmussen, Fay Probert, Dorte A Olsen, Jonna S Madsen, Jesper Eugen-Olsen, Thomas Peter Enggaard, Claus Varnum, Kate L Lambertsen, Daniel C Anthony, Morten Rune Blichfeldt-Eckhardt","doi":"10.1186/s13075-026-03839-1","DOIUrl":"10.1186/s13075-026-03839-1","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis is a leading cause of pain and disability, yet the biological processes linking peripheral joint pathology with central pain mechanisms and wider symptom burden remain poorly defined.</p><p><strong>Methods: </strong>We performed an integrated metabolomic and inflammatory analysis of cerebrospinal fluid and serum obtained from patients with osteoarthritis (n = 81) and healthy pain-free controls (n = 70). Proton nuclear magnetic resonance spectroscopy was used for metabolomic profiling, alongside targeted protein assays for inflammatory mediators. Orthogonal partial least squares discriminant analysis was applied to assess separation between groups and to determine diagnostic accuracy. Associations between metabolites and clinical outcomes, including pain intensity, disability and sleep disturbance, were examined, with adjustment for age and BMI.</p><p><strong>Results: </strong>Clear separation between osteoarthritis and healthy pain-free control participants was observed in both biofluids, with classification accuracies of 87% for serum and 89% for cerebrospinal fluid. Reduced serum histidine, glutamine, albumin (lysyl) and lysine distinguished osteoarthritis from healthy controls. In cerebrospinal fluid, osteoarthritis was characterised by higher lactate and glutamate and lower glucose and glutamine compared to controls. Combining metabolomic data with inflammatory proteins increased diagnostic accuracy to 90% and remained significant after matching for age and BMI. Reductions in serum histidine and glutamine were consistent across subgroups, including stratification by pain severity. These metabolites correlated inversely with pain intensity, disability, sleep disturbance and overall symptom impact, and were more markedly altered in women, who also reported greater symptom burden.</p><p><strong>Conclusions: </strong>Osteoarthritis is associated with a distinct pattern of peripheral and central metabolic disturbance. Histidine and glutamine emerge as promising biomarkers related to pain and clinical severity, highlighting metabolic pathways as potential targets for improved stratification and intervention in osteoarthritis pain.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation inhibitor decitabine ameliorates spondyloarthritis by suppressing Th17 responses and epigenetically upregulating VIPR1 in SKG mice.","authors":"Hoshiko Furusawa, Goh Murayama, Masaki Nojima, Taiga Kuga, Yukitomo Hagiwara, Yoshiyuki Abe, Makio Kusaoi, Kurisu Tada, Ken Yamaji, Naoto Tamura","doi":"10.1186/s13075-026-03848-0","DOIUrl":"10.1186/s13075-026-03848-0","url":null,"abstract":"<p><strong>Background: </strong>Spondyloarthritis (SpA) is a chronic inflammatory disorder characterized by enthesitis of axial and peripheral joints. Although genetic factors, bacterial infection, dysbiosis, and mechanical stress contribute to its development, the role of epigenetic regulation remains poorly understood. DNA methylation has been implicated in immune dysregulation, and the DNA methyltransferase inhibitor, decitabine (DAC), has demonstrated therapeutic effects in autoimmune disease models. This study aimed to evaluate the effect of DAC in the SpA-resembling SKG/Jcl (SKG) mouse model and elucidate the immunological mechanisms.</p><p><strong>Methods: </strong>SpA-like arthritis was induced in SKG mice via intraperitoneal injection of curdlan (1,3-β-glucan aggregates). DAC (1 mg/kg) was administered weekly. Arthritis severity and histopathological changes were evaluated in the limb joints and tail, and histopathological enthesitis scores were assessed in the limb joints. Splenic T-cell profiles were analyzed by flow cytometry. CD4⁺ T cells were stimulated in vitro with DAC to assess cytokine production. To investigate epigenetic regulation, reduced representation bisulfite sequencing (RRBS) and RNA-seq were performed on Achilles tendon tissue containing enthesis. Local expression of IL-17 and vasoactive intestinal peptide receptor 1 (VIPR1) in peripheral entheses was assessed by immunohistochemistry.</p><p><strong>Results: </strong>DAC treatment significantly reduced arthritis severity and improved histopathological findings, including synovial hyperplasia, inflammatory cell infiltration, bone erosion, and cartilage loss. Peripheral enthesitis at the Achilles tendon insertion sites was also reduced. Flow cytometric analysis demonstrated that the DAC-treated group reduced IL-17 A expression in splenic CD4⁺ T cells during the early phase (weeks 4-8) and decreased PD-1 expression in regulatory T cells (Tregs) at week 12. In vitro, DAC suppressed IL-17 A secretion and enhanced TGF-β production in stimulated splenic CD4⁺ T cells. Integrated RRBS and RNA-seq analyses identified Vipr1 as a DAC-responsive gene, showing significant hypomethylation (Δmethylation ≥ - 25%) and concordant transcriptional upregulation (log₂FC > 1) in the entheses of DAC-treated mice. Immunohistochemical analysis of the ankle entheses revealed decreased IL-17 A expression and increased VIPR1 expression.</p><p><strong>Conclusions: </strong>DAC ameliorated SpA in SKG mice, possibly through suppression of Th17 responses and epigenetic upregulation of Vipr1, and may be associated with improved Treg-associated regulation. These findings highlight an important role of DNA methylation in SpA pathogenesis.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-inflammatory potential of nicotinamide (vitamin B3) in JIA: modulating Treg numbers and function with nicotinamide.","authors":"Lotte Nijhuis, Rianne C Scholman, Arief Lalmohamed, Sebastiaan J Vastert, Jorg van Loosdregt","doi":"10.1186/s13075-026-03846-2","DOIUrl":"10.1186/s13075-026-03846-2","url":null,"abstract":"<p><strong>Background: </strong>Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic disease in children and is characterized by chronic joint inflammation driven by immune dysregulation. A disturbed regulatory T (Treg) cell-effector T cell axis has been demonstrated in these patients which contributes to a dysregulated immune tolerance in JIA. Therefore, strategies to enhance Treg numbers and suppressive capacity to restore immune homeostasis represent a promising therapeutic approach. Nicotinamide (NAM), a form of vitamin B₃ and precursor of nicotinamide adenine dinucleotide (NAD⁺), has emerged as an immunomodulator capable of promoting Treg cell function.</p><p><strong>Methods: </strong>Here, we investigate the effects of NAM on Treg percentages and suppressive capacity in mononuclear cells derived from peripheral blood (PBMCs) and synovial fluid of JIA patients (SFMCs). In an exploratory pilot phase II clinical study, NAM concentrations were measured in paired blood plasma and SF from 6 JIA patients after oral administration of daily 1.8 g/m² for three days.</p><p><strong>Results: </strong>NAM treatment significantly increased the proportion of FOXP3-expressing CD4⁺ T cells in both PBMCs and SFMCs and Treg suppressive capacity in PBMCs from healthy controls in vitro. Comparable NAM concentrations were detected in plasma and SF following oral administration, demonstrating its ability to penetrate the inflamed joint environment.</p><p><strong>Conclusion: </strong>Given its established safety in both adults and children, NAM represents a promising future candidate for adjunctive therapy in JIA by restoring the balance between regulatory and effector T cells. Further clinical and mechanistic studies are warranted to define optimal dosing regimens and its place in the long-term treatment strategy of JIA.</p><p><strong>Trial registration: </strong>Assessing penetration of high dose nicotinamide (Vitamin B3) in synovial fluid. EudraCT Number: 2018-002245-11, start date Jan 16th, 2019.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sputum lautropia is decreased in rheumatoid arthritis-associated pulmonary fibrosis.","authors":"Timothy M Wilson, Brendan Allen, J Kirk Harris, Kristine A Kuhn, Kevin D Deane, Stephen M Humphries, Joyce S Lee, Joshua J Solomon, M Kristen Demoruelle","doi":"10.1186/s13075-026-03845-3","DOIUrl":"10.1186/s13075-026-03845-3","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether lung microbial composition differs between individuals with rheumatoid arthritis and pulmonary fibrosis (RA-PF) compared to those without fibrosis (RA-no-PF).</p><p><strong>Methods: </strong>We enrolled 54 RA patients (22 RA-PF, 32 RA-no-PF) from rheumatology and pulmonary clinics. PF was defined by high-resolution computed tomography (HRCT) findings. Induced sputum was analyzed using 16 S rRNA sequencing to identify the relative abundance of sputum bacteria. Taxonomic differences between groups were evaluated using three independent analytic approaches: Mann-Whitney U, DESeq2, and EdgeR, with false discovery rate correction. Logistic regression examined associations between Lautropia abundance and clinical variables.</p><p><strong>Results: </strong>Individuals with RA-PF were older, more often male, and had a higher history of smoking than those with RA-no-PF. Alpha diversity was lower in RA-PF, while beta diversity did not differ between groups. Across the three analytic methods, Lautropia consistently showed decreased abundance in RA-PF compared to RA-no-PF. In multivariable models adjusting for age, sex, and smoking, RA-PF remained independently associated with undetectable levels of Lautropia (OR = 0.14, p = 0.023). Within RA-PF, when Lautropia was undetectable, there was no difference in pulmonary physiology but did show a trend towards more lung fibrosis.</p><p><strong>Conclusion: </strong>Sputum Lautropia is significantly reduced in RA-PF, and its absence may correlate with more severe fibrosis. These findings support a potential role for the lung microbiome in the pathogenesis of pulmonary fibrosis and raise the possibility that commensal taxa such as Lautropia modulate fibrotic pathways. Longitudinal and mechanistic studies are needed to determine whether Lautropia depletion precedes fibrosis and whether microbial-directed approaches represent new therapeutic avenues in RA.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular classification of primary Sjögren's syndrome based on salivary gland omics.","authors":"Wuwei Zhuang, Qi Zhang, Jie Shen, Lin Zhu, Wenyan Shen, Xinyu Pu, Tingting Yan, Qiao Ye","doi":"10.1186/s13075-026-03843-5","DOIUrl":"10.1186/s13075-026-03843-5","url":null,"abstract":"<p><p>Primary Sjögren's syndrome is a complex and heterogeneous disease, often involving multiple organ systems and carrying an increased risk of lymphoma development. In this study, we integrated single-cell RNA sequencing and bulk RNA-seq data to deconvolute the disease heterogeneity using non-negative matrix factorization.This analysis identified four distinct molecular subtypes, which we designated as the Classical Immune Type, Ion Channel Type, Fibrotic Senescent Type, and Immune Desert Type. Through differential expression analysis, we further identified characteristic gene sets for each of these subtypes. The Gene Set Variation Analysis scores of these subtype-specific gene signatures in patient minor salivary gland RNA-seq data may potentially inform patient stratification. We preliminarily characterized the clinical features and local immune microenvironment profiles associated with each subtype. These findings may have implications for personalized therapeutic strategies and potentially inform the selection of patients for future clinical trials.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13465307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent antibiotic exposure and response to treatment of juvenile idiopathic arthritis: a retrospective cohort study.","authors":"Daniel B Horton, Charu Verma, Sanika Rege, Stephen Crystal, Tobias Gerhard, Alicia Iizuka, Matthew Iozzio, Dawn Koffman, Lauren E Parlett, Julianne Varga, Carlos D Rose, Brian L Strom","doi":"10.1186/s13075-026-03842-6","DOIUrl":"10.1186/s13075-026-03842-6","url":null,"abstract":"<p><strong>Background: </strong>Juvenile idiopathic arthritis (JIA) has been tied to microbiome disruption and antibiotic exposure. Gut microbiota may affect how adults with rheumatoid arthritis respond to methotrexate. We tested if exposure to antibiotics was associated with response to methotrexate for JIA.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using national US public and private insurance claims data (2001-2023). We included children ages 1-17 continuously enrolled for ≥ 10 months and diagnosed with JIA who initiated methotrexate monotherapy or, for comparison, tumor necrosis factor inhibitor (TNFi) monotherapy without prior disease-modifying antirheumatic drug (DMARD) exposure. Antibiotic exposure during the 10-month baseline period was characterized by number of courses, timing, and type. The primary outcome was initiation of a second DMARD after ≥ 30 days (proxy of treatment ineffectiveness). Associations between antibiotic exposure and treatment change were estimated using Cox regression, adjusting for database and baseline demographic, disease, treatment, and health utilization covariates, and represented by adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). In additional analyses, we examined differences based on JIA category (juvenile spondyloarthritis vs. others), outcome specification, and follow-up starting up to 90 days after initial DMARD exposure.</p><p><strong>Results: </strong>We identified 6,135 new methotrexate users (54.4% antibiotic-exposed) and 1,554 new TNFi users (49.5% antibiotic-exposed), among whom approximately 20% experienced the primary outcome over 10 months of follow-up. No relationships were observed between pre-DMARD antibiotic exposure and DMARD changes in methotrexate users (aHR 1.01, 95% CI 0.90, 1.13) or TNFi users (aHR 1.10, 95% CI 0.86, 1.40). Number of antibiotic courses, antibiotic timing, and type of antibiotic exposure, as well as nonbacterial antimicrobial drug exposure, were also not associated with treatment changes in methotrexate or TNFi users. Findings based on JIA category, alternative outcome definitions, and delayed start of follow-up were consistent.</p><p><strong>Conclusions: </strong>Recent antibiotic exposure is not associated with changes in DMARD treatment in children with JIA. This finding is reassuring for a population with higher risks for serious infections than other children and with high rates of antibiotic exposure.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13464929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}