Annals of the Rheumatic Diseases最新文献

{"title":"Development of salivary gland organoids derived from patient biopsies: a functional model of Sjögren's disease.","authors":"Loïc Meudec, Negaar Goudarzi, Sacha E Silva-Saffar, Juliette Pascaud, Fanny Jaulin, Quentin Pascal, Thierry Lazure, Rami Bechara, Xavier Mariette, Gaetane Nocturne","doi":"10.1016/j.ard.2025.04.020","DOIUrl":"10.1016/j.ard.2025.04.020","url":null,"abstract":"<p><strong>Objectives: </strong>Salivary gland epithelial cells (SGECs) play a key role in Sjögren's disease (SjD) as an active contributor to the pathogenesis. Current models lack clear epithelial readouts. Our aim was to establish a more advanced model by developing salivary gland organoids (SGOs) from labial salivary gland biopsies (LSGBs) of SjD patients and sicca controls.</p><p><strong>Methods: </strong>We included SjD patients fulfilling the American College of Rheumatology/European League Against Rheumatism 2016 criteria and sicca controls. LSGBs were dissociated, encapsulated in extracellular matrix, and submerged in growth expansion medium for long-term culture. SGOs were primarily cultured in differentiation medium and then transferred to a low attachment plate to form differentiated SGOs (DIF-SGOs).</p><p><strong>Results: </strong>We included 13 SjD and 15 controls. In both groups, SGOs were formed, demonstrating long-term culture viability and comparable self-renewal capacity (3.3 ± 1.7 months). DIF-SGOs comparably exhibited mature acinar (aquaporin 5, amylase), ductal (cytokeratins 5 and 7) and myoepithelial (α-smooth muscle actin) markers in both groups. DIF-SGOs were responsive to inflammation by expressing BAFF, CXCL10 and IL7 upon stimulation with poly(I:C) and interferon-α. DIF-SGOs also demonstrated a swelling response to cholinergic stimulation by pilocarpine. We observed significant differences between SjD- and control-derived SGOs. Notably, SjD-derived DIF-SGOs consistently maintained a persistent interferon signature throughout long-term culture. In addition, the swelling capacity was reduced in SjD-derived DIF-SGOs compared to control. However, treatment with tofacitinib enhanced the swelling ability, suggesting a potential effect on saliva production.</p><p><strong>Conclusions: </strong>We successfully developed SGOs from LSGBs of SjD patients, allowing long-term culture and faithfully recapitulating the disease phenotype. This model holds promise as a valuable tool for drug screening.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1195-1206"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remote monitoring or patient-initiated care in axial spondyloarthritis: a 3-armed randomised controlled noninferiority trial.","authors":"Inger Jorid Berg, Eirik K Kristianslund, Anne Therese Tveter, Joseph Sexton, Gunnstein Bakland, Laure Gossec, Sarah Hakim, Gary J Macfarlane, Ellen Moholt, Sella Aarrestad Provan, Emil E Kvernberg Thomassen, Annette de Thurah, Espen A Haavardsholm, Siri Lillegraven, Nina Osteras","doi":"10.1016/j.ard.2025.04.019","DOIUrl":"10.1016/j.ard.2025.04.019","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to determine whether novel follow-up regimen, remote monitoring, or patient-initiated care is noninferior to usual care in maintaining low disease activity, in patients with axial spondyloarthritis (axSpA).</p><p><strong>Methods: </strong>This is a randomised, controlled, 3-armed, parallel-group, open-label, noninferiority trial. Patients with axSpA in low disease activity on stable treatment with tumour necrosis factor inhibitor were recruited from a Norwegian outpatient clinic. Patients were randomly allocated 1:1:1 to remote monitoring, patient-initiated care, or usual care (control group), with 18 months of follow-up. Primary outcome was mean probability of axSpA Disease Activity Score (ASDAS) of <2.1, compared between groups at 6, 12, and 18 months, with 15% noninferiority margin. Secondary outcomes included other measures of disease activity, physical function, patient satisfaction, change of medication, resource use, and adverse events.</p><p><strong>Results: </strong>Of 243 patients enrolled patients, 235 completed the study (remote monitoring = 75, patient-initiated care = 79, usual care = 81). At the 6-month, 12-month, and 18-month assessments, 90% or more patients in all 3 groups had ASDAS of <2.1. The estimated difference of probability of ASDAS < 2.1 was as follows: usual care vs remote monitoring, -4.1% (97.5% CI, -9.9% to 1.8%); usual care vs patient-initiated care, -1.1% (97.5% CI, -7.2% to 4.9%); and remote monitoring vs patient-initiated care, 2.9% (95% CI, -1.5% to 7.4%). Health providers' resource use was lowest in patient-initiated care; other secondary outcomes were comparable.</p><p><strong>Conclusions: </strong>In patients with axSpA in low disease activity and on stable treatment with tumour necrosis factor inhibitor, follow-up with remote monitoring or patient-initiated care was noninferior to usual care in maintaining low disease activity, supporting the implementation of novel follow-up strategies.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1140-1150"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel IgG and IgA autoantibodies validated in two independent cohorts are associated with disease activity and determine organ manifestations in systemic lupus erythematosus: implications for anti-LIN28A, anti-HMGN5, anti-IRF5, and anti-TGIF1.","authors":"Julius Lindblom, Denis Lagutkin, Natalia Sherina, Helena Idborg, Lorenzo Beretta, Maria Orietta Borghi, Janique M Peyper, Guillermo Barturen, Per-Johan Jakobsson, Marta E Alarcón-Riquelme, Dionysis Nikolopoulos, Ioannis Parodis","doi":"10.1016/j.ard.2025.04.008","DOIUrl":"10.1016/j.ard.2025.04.008","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>Plasma samples were screened for IgG and IgA seroreactivity against 1609 protein autoantigens using a microarray (i-Ome Discovery; Sengenics). We determined differentially abundant autoantibodies (daAAbs) in patients with SLE vs healthy controls within a discovery (n = 196 vs n = 110; NTC02890121) and an independent validation cohort (n = 30 vs n = 83; NCT02890134) from the European PRECISESADS project. Validated daAAbs were analysed in relation to global and organ-specific disease activity using linear and logistic regression, along with daAAb target pathway enrichment analysis.</p><p><strong>Results: </strong>We validated 89 IgG and 66 IgA daAAbs. IgG anti-LIN28A, IgG anti-HMGN5, and both isotypes for anti-IRF5 and anti-TGIF1 were associated with a SLE disease activity index 2000 score of ≥10, negatively associated with lupus low disease activity state, and highly prevalent in subgroups with active disease across organ manifestations. IgG anti-LIN28A levels exceeded the cutoff for positivity in 53% of patients with central nervous system (CNS) involvement, a prevalence higher than that observed for anti-double-stranded DNA (20%) and 47% of patients with renal activity. A cluster of IgG and IgA daAAbs against RNA-binding proteins, including anti-LIN28A, was linked to CNS involvement. IgA anti-FOSL2 was elevated uniquely in patients with musculoskeletal activity. Enriched pathways involving DNA binding and repair showed considerable overlap across manifestations.</p><p><strong>Conclusions: </strong>Novel IgG and IgA autoantibodies, including IgG anti-LIN28A, IgG anti-HMGN5, IgG and IgA anti-IRF5, and IgG and IgA anti-TGIF1 were associated with SLE disease activity and highly abundant across organ manifestations.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1164-1179"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional dissection of noncoding variants associated with rheumatoid arthritis.","authors":"Ajay Jajodia, Arpit Mishra, Naresh Doni Jayavelu, Katharina Lambert, Nicholas Moss, Zongchen Yang, Karen Cerosaletti, Jane H Buckner, R David Hawkins","doi":"10.1016/j.ard.2025.04.001","DOIUrl":"10.1016/j.ard.2025.04.001","url":null,"abstract":"<p><strong>Objectives: </strong>Noncoding variants are critical to our understanding of the genetic basis of diseases and disorders such as rheumatoid arthritis (RA). While genome-wide association studies have identified regions of the genome associated with disease, functional studies are still lagging that can identify potentially causative variants.</p><p><strong>Methods: </strong>In order to functionally fine-map RA-associated variants, we identified variants at enhancers marked in primary activated T helper cells and conducted massively parallel reporter assay in these cells.</p><p><strong>Results: </strong>We found that combinations of functional variant genotypes are often exclusive to patients with RA. We leveraged 3-dimensional genome architecture and expression quantitative trait loci data to identify target genes of enhancers exhibiting allelic differences in activity. We confirmed enhancer activity and target gene interactions by Clustered Regularly Interpaced Short Palindromic Repeats Cas9 (CRISPR-Cas9) deletion in primary T cells.</p><p><strong>Conclusions: </strong>The identification of functional enhancer variants suggests possible causal variants, and their target genes reveal known and novel genes as likely drivers of RA, as well as a means for therapeutic intervention.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1117-1129"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-year remission of therapy-resistant SLE after a single course with the bispecific CD3: BCMA antibody teclistamab, but induction of a non-infectious Crohn's-like inflammatory bowel disease.","authors":"Hanns-Martin Lorenz, Wolfgang Merkt, Juliane Brandt, Thomas Giese, Tarik Exner, Norbert Blank, Margarida Souto-Carneiro, Annika Gauss, Marc S Raab","doi":"10.1016/j.ard.2025.05.007","DOIUrl":"10.1016/j.ard.2025.05.007","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1277-1279"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitopes targeted by autoantibodies in presymptomatic individuals predict early rheumatoid arthritis.","authors":"Yibo He, Outi Sareila, Linda Johansson, Monica Leu Agelii, Lei Cheng, Anders Lundquist, Erik Lönnblom, Gerdur Gröndal, Bjorn Gudbjornsson, Kim Hørslev-Petersen, Jon Lampa, Kristina Lend, Merete Lund Hetland, Dan Nordström, Michael Nurmohamed, Anna Rudin, Till Uhlig, Mikkel Østergaard, Inger Gjertsson, Solbritt Rantapää-Dahlqvist, Rikard Holmdahl","doi":"10.1016/j.ard.2025.04.013","DOIUrl":"10.1016/j.ard.2025.04.013","url":null,"abstract":"<p><strong>Objectives: </strong>To determine anticitrullinated protein antibody (ACPA) responses to novel peptides predicting the clinical outcomes of treatment-naïve early rheumatoid arthritis (RA) in the presymptomatic stage.</p><p><strong>Methods: </strong>We analysed monoclonal ACPAs derived from RA patients, including a characterised protective ACPA (clone E4), along with plasma samples collected from 520 presymptomatic individuals, of whom 244 were also sampled at diagnosis of RA, and 530 population controls in Sweden. The validation cohort (The Nordic Rheumatic Diseases Strategy Trials and Registries, NORD-STAR) consisted of 690 treatment-naïve early RA patients. Responses to citrullinated or native alpha-enolase (ENO1) or peptidylarginine deiminase 4 (PAD4) peptides were analysed by bead-based multiplex flow immunoassay. Clinical outcomes included C-reactive protein (CRP) and the 28-joint disease activity score (DAS28) with its components: tender joint count (TJC), swollen joint count (SJC), and erythrocyte sedimentation rate (ESR).</p><p><strong>Results: </strong>Monoclonal ACPAs displayed distinct binding patterns to ENO1 and PAD4 peptides. A time-dependent increase of ACPA response to citrullinated peptides was observed in the presymptomatic stage towards onset. In the presymptomatic (0.2-5 years before onset) and early RA stage, ACPA responses to several ENO1 and PAD4 peptides were associated with less severe RA, assessed as lower levels of CRP and DAS28 and its components. In early RA, the association was more pronounced in rheumatoid factor (RF)-negative patients based on lower SJC. In presymptomatic individuals, ACPA responses widely predicted lower disease activity in early RA and were more pronounced in 5 selected peptides.</p><p><strong>Conclusions: </strong>Antibody responses to certain citrullinated epitopes are associated with lower disease activity in treatment-naïve early RA and appear years before symptom onset of RA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1090-1103"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analysis reveals the multilateral inflammatory mechanisms of CD14 monocytes in gout.","authors":"Ahmed Alaswad, Georgiana Cabău, Tania O Crişan, Liang Zhou, Martijn Zoodsma, Javier Botey-Bataller, Wenchao Li, Cristina Pamfil, Mihai G Netea, Tony Merriman, Cheng-Jian Xu, Yang Li, Leo A B Joosten","doi":"10.1016/j.ard.2025.01.046","DOIUrl":"10.1016/j.ard.2025.01.046","url":null,"abstract":"<p><strong>Objectives: </strong>Gout, prevalent inflammatory arthritis caused by urate crystal deposition, involves immune cell activation, yet the precise role of CD14 monocytes in initiating the inflammatory response is poorly understood. This study aimed to characterise the molecular and cellular landscape of CD14 monocytes in gout using single-cell transcriptomic analysis.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was performed on peripheral blood mononuclear cells from 8 gout patients and 6 age- and sex-matched healthy controls. The findings were validated using publicly available datasets. Differential gene expression and pathway enrichment analyses were conducted to identify gout's key molecular regulators and cellular subclusters.</p><p><strong>Results: </strong>At the molecular level, we identified hypoxia-related pathways, including HIF1A, as key regulators of interleukin-1β production in CD14 monocytes in gout. We also observed significant downregulation of CLEC12A across all CD14 monocyte subclusters. At the cellular level, an S100A^high CD14 monocyte subcluster, characterized by high expression of S100A8/A9/A12 and linked to inflammatory and metabolic pathways, was found to drive NLRP3 and CLEC7A inflammasome activation, as well as prostaglandin secretion. In vitro stimulation with monosodium urate crystals revealed that the differentially expressed genes were enriched in S100A^high monocytes, highlighting the synergistic role of these pathways in driving gout inflammation. Additionally, gout genome-wide association study-prioritised genes underscored the role of fatty acid metabolism in inflammation, promoting prostaglandin secretion from S100A^high monocytes.</p><p><strong>Conclusions: </strong>These findings provide new insights into the role of CD14 monocytes in gout pathogenesis, particularly the contribution of hypoxia and fatty acid metabolism pathways, and suggest potential therapeutic targets for precision medicine in gout treatment.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1253-1263"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prospective Registry of MyositIS (PROMIS): I. Next-generation sequencing identifies HLA-DQA1 as a novel genetic risk of anti-MDA5 antibody-positive dermatomyositis.","authors":"Xinzhuang Yang, Chen Yu, Xiuling Zhang, Chanyuan Wu, Zhao Peng, Yixuan Gai, Jinmin Peng, Shuang Zhou, Lan Song, Hui Huang, Dong Xu, Jiuliang Zhao, Xinping Tian, Xinwang Duan, Xiaofeng Zeng, Mengtao Li, Qian Wang","doi":"10.1016/j.ard.2025.02.017","DOIUrl":"10.1016/j.ard.2025.02.017","url":null,"abstract":"<p><strong>Objectives: </strong>Antimelanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5⁺ DM) is a rare subtype of myositis with a poor prognosis and insufficient genetic understanding. Our study aimed to identify risk variants associated with anti-MDA5⁺ DM and to assess their correlation with clinical outcomes.</p><p><strong>Methods: </strong>We enrolled 231 anti-MDA5⁺ DM patients, 127 anti-MDA5⁻ DM patients, 1468 patients with non-DM rheumatic disease, and 1027 healthy controls, with an additional 51 anti-MDA5⁺ DM patients for validation. Whole-exome sequencing was used to identify human leukocyte antigen (HLA) alleles, amino acids, and single nucleotide polymorphisms (SNPs) in major histocompatibility complex (MHC) and non-MHC regions. Association studies were performed to identify genetic variants associated with anti-MDA5⁺ DM by comparing different sets of control groups. A clinical association study was conducted to further explore the influence of genetic factors on clinical manifestations.</p><p><strong>Results: </strong>Two novel genetic risks, HLA-DQA1*06:01 and HLA-DQB1*06:09, were significantly associated with anti-MDA5⁺ DM in both the discovery and validation cohorts. HLA-DQA1*06:01 was particularly prevalent in anti-MDA5⁺ DM (20.4%) compared with anti-MDA5⁻ DM (6.69%) and non-DM rheumatic disease (5.93%). Besides, the strongest associated amino acid was HLA-DQα1:69 (P = 3.27 × 10^-11), and 1 SNP in the ARHGAP22 gene (rs76208937) showed suggestive significance (P = 7.99 × 10^-6). In addition, HLA-DQA1*06:01 was linked to acute rapidly progressive interstitial lung disease (P < .001), elevated levels of lactate dehydrogenase (P = .026), and death (P = .049) in patients with anti-MDA5⁺ DM.</p><p><strong>Conclusions: </strong>HLA-DQA1*06:01 is a new genetic and prognostic factor for anti-MDA5⁺ DM, potentially serving as a biomarker for early diagnosis and intervention.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1221-1230"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD4+ tissue-resident memory Th17 cells are a major source of IL-17A in Spondyloarthritis synovial tissue.","authors":"Feng Liu, Hui Shi, Jason D Turner, Rachel Anscombe, Jiaqi Li, Takuya Sekine, Ariane Hammitzsch, Devika Agarwal, Christopher Mahony, Jiewei Chen, Ben Kendrick, Dajiang Du, Qiang Tong, Lihua Duan, Kyla Dooley, Hai Fang, Ilya Korsunsky, Roopa Madhu, Adam P Cribbs, Matthias Friedrich, Brian D Marsden, Yi-Ling Chen, Graham Ogg, Anna Adams, Warner Chen, Steven Leonardo, Fiona E McCann, Christopher D Buckley, Terence Rooney, Thomas Freeman, Holm H Uhlig, Calliope Dendrou, Adam Croft, Andrew Filer, Paul Bowness, Liye Chen","doi":"10.1016/j.ard.2025.04.018","DOIUrl":"10.1016/j.ard.2025.04.018","url":null,"abstract":"<p><strong>Objectives: </strong>Interleukin (IL)-17A is a key driver of spondyloarthritis (SpA) joint pathology. We aimed to identify its cellular source in synovial tissue from patients with 2 forms of SpA, namely axial SpA (AxSpA) and psoriatic arthritis (PsA).</p><p><strong>Methods: </strong>Synovial tissue from patients with SpA was profiled using single-cell RNA sequencing (scRNA-seq; AxSpA, n = 5; PsA, n = 6) or spatial RNA profiling (PsA, n = 4). CellPhoneDB was used to infer cell-cell communication. Tissue-resident memory Th17 (TRM17)-like cells were generated in vitro using blood memory CD4+ T cells from SpA patients. An epigenetic inhibitor library, siRNA, and clustered regularly interspaced short palindromic repeats (CRISPR) were used to identify epigenetic regulator(s) for TRM17.</p><p><strong>Results: </strong>scRNA-seq showed that CD4+CXCR6+ TRM17 cells are the predominant spontaneous IL17A producers in SpA synovium. Cell-cell communication and single-cell spatial analysis support the interaction between TRM17 and CLEC10A+ dendritic cells, which were activated in SpA. Both sublining and lining fibroblasts in SpA synovium showed evidence of interleukin (IL)-17A activation. In vitro-generated CD4+ TRM17-like cells phenocopied joint tissue TRM17, producing IL-17A/F upon T cell-receptor (TCR) stimulation, which was further enhanced by cytokines. Perturbation of BRD1 inhibited the generation of TRM17-like cells.</p><p><strong>Conclusions: </strong>CD4+ TRM17 cells are the predominant source of IL-17A in SpA synovial tissue. TCR stimulation is essential for the secretion of IL-17A by CD4+TRM17-like cells. The epigenetic regulator bromodomain-containing protein 1 (BRD1) contributes to the generation of CD4+TRM17. Depleting CD4+TRM17 cells in SpA is thus a therapeutic strategy with potential to induce long-term remission.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1151-1163"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective use of anti-CD19 chimeric antigen receptor T cells in a case of treatment-resistant granulomatosis with polyangiitis.","authors":"Luisa Uhlmann, Matthias Pierer, Marco Krasselt, Georg Franke, Robert Zeidler, Osama Sabri, Timm Denecke, Ulrich Sack, Ulrike Köhl, Andreas Boldt, Dominic Borie, Ulf Wagner, Uwe Platzbecker, Vladan Vucinic","doi":"10.1016/j.ard.2025.04.029","DOIUrl":"10.1016/j.ard.2025.04.029","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1280-1283"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}