Annals of the Rheumatic Diseases最新文献

{"title":"AYLo study-elevated relapse risk and dysregulated proinflammatory signalling in giant cell arteritis patients with mosaic loss of the Y chromosome.","authors":"Simon M Petzinna, Sophie-Marie Kirch, Maike S Adamson, De Xi, Claus-Jürgen Bauer, Lena Kreis, Reza Gheitasi, Pantelis Karakostas, Rayk Behrendt, Georg Nickenig, Sebastian Zimmer, Raul N Jamin, Valentin S Schäfer","doi":"10.1016/j.ard.2025.06.2133","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2133","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the prevalence of mosaic loss of the Y chromosome (mLOY) in giant cell arteritis (GCA) and its impact on disease activity.</p><p><strong>Methods: </strong>Patients diagnosed with GCA were prospectively recruited, and their leukocyte mLOY burden was analysed. The optimal mLOY threshold for predicting relapse was determined using the receiver operating characteristic curve and Youden index. Relapse-free survival was assessed using Kaplan-Meier analysis with the log-rank test. Levels of selected proinflammatory cytokines were quantified using a multiplex array.</p><p><strong>Results: </strong>A total of 74 GCA patients were enrolled (mean, 76.0 years; SD, 10.7). At inclusion, 25.7% (19/74) of patients exhibited active disease. Relapses occurred in 23.0% of patients. The median mLOY burden was 17.8% (SD, 23.7%). An optimal threshold of 10.2% was identified for predicting relapse. Patients exceeding this cutoff had a significantly higher relapse risk (P < .001) with a shorter relapse-free survival (647 vs 992 days; P < .001). Multivariable Cox regression confirmed mLOY >10.2% as an independent predictor of relapse (hazard ratio, 17.4; 95% CI, 3.5-86.0; P = .003). In multiplex analysis, mLOY was positively associated with interleukin (IL)-6 (P = .045; r = 0.24) across the cohort, with elevated IL-6 levels in remission patients with mLOY >10.2% (P = .010). In patients undergoing IL-6 receptor inhibitor treatment and in remission, mLOY was significantly positively associated with IL-6 (P = .002; r = 0.54) and IL-17A (P = .026; r = 0.40).</p><p><strong>Conclusions: </strong>This study is the first to identify mLOY as a strong, independent predictor of relapse risk and to link mLOY with modulated proinflammatory signalling in GCA. Our findings suggest mLOY as a prognostic biomarker and underscore its possible role in the pathophysiology of GCA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641603","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":"Effects of different B-cell-depleting strategies on the lymphatic tissue.","authors":"Carlo Tur, Markus Eckstein, Laura Bucci, Janina Auth, Christina Bergmann, Simon Rauber, Melanie Hagen, Danae-Mona Nöthling, Sebastian Böltz, Andreas Wirsching, Koray Tascilar, Filippo Fagni, Giulia Corte, Aleix Rius Rigau, Yi Qin, Panagiotis Garantziotis, Jule Taubmann, Jochen Wacker, Andreas Ramming, Maria Antonietta D Agostino, Sebastian Rauch, Arndt Hartmann, Fabian Müller, Andreas Mackensen, Ricardo Grieshaber-Bouyer, Georg Schett, Aline Bozec, Maria Gabriella Raimondo","doi":"10.1016/j.ard.2025.06.2120","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2120","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the efficacy of new protein-based B cell depletion with glyco-engineered anti-CD20 antibody obinutuzumab (OBI) and the CD19/CD3 T cell engager blinatumomab (BLI) in patients with autoimmune diseases (AIDs) in comparison to rituximab (RTX) and CD19 chimeric antigen receptor (CAR) T cell therapy.</p><p><strong>Methods: </strong>Sequential inguinal lymph node biopsies were taken before and after treatment with OBI-, BLI-, RTX- and CD19-CAR T cells in patients with AID. CD19+ and CD20+ B cells, plasma cells, T cells and macrophages were analysed by immunohistochemistry. Changes in follicular architecture (follicular dendritic cells, T follicular helper cells, proliferation) were also assessed.</p><p><strong>Results: </strong>Baseline and follow-up lymph node biopsies from 24 patients with AID (OBI, 4; BLI, 4; RTX, 4; CD19-CAR T cells, 12) were analysed. B cell depletion was confirmed in all CD19-CAR T cell-treated patients but only in 1 (OBI) out of 12 protein-based B cell-treated patients. Likewise, follicular architecture was disrupted in all CD19-CAR T cell-treated patients but only in 1 (OBI) out of 12 protein-based B cell-treated patients. B cell depletion efficacy in the lymph nodes was 100% for CD19-CAR T cells, 92% for OBI, 86% for RTX and 69% for BLI. Plasma cells were reduced but not depleted in all treatment approaches. CD3+ T cells and CD68+ macrophages remained unaffected. Peripheral blood B cell depletion occurred in all but 1 BLI-treated patient. B cell depletion was associated with stable drug-free remission, whereas a reduction in B cell numbers without depletion required retreatment with immunomodulatory drugs.</p><p><strong>Conclusions: </strong>Protein-based B cell depletion reduces but usually does not deplete B cells in lymph nodes leaving the follicular architecture intact and being associated with disease recurrence.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616033","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":"Quantified intakes of key diet components and the risk of developing rheumatoid arthritis: Results from a nested case-control study.","authors":"Rebecka Bäcklund, Ulf Bergström, Michele Compagno, Linnea Arvidsson, Emil Rydell, Emily Sonestedt, Carl Turesson","doi":"10.1016/j.ard.2025.06.2123","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2123","url":null,"abstract":"<p><strong>Objectives: </strong>This nested case-control study aimed to investigate the relationship between components of the Swedish food-based dietary guidelines (SDG) from 2015 and the risk of developing rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>Data were obtained from the prospective Malmö Diet and Cancer Study (MDCS) conducted 1991-1996. Diet was assessed at baseline using a validated diet history method. Incident RA cases until 2016 were identified through register linkage, followed by a validation process through review of medical records. For each case, 4 RA-free controls, matched for age, sex, and year of inclusion in the MDCS, were selected from the cohort. Adherence to the SDG was assessed using the SDG Score (SDGS) of 5 components. Multivariable logistic regression and restricted cubic splines (RCS) were applied to analyse the relationships among the SDGS, its components, and RA.</p><p><strong>Results: </strong>A total of 305 incident RA cases (67% rheumatoid factor/anti-cyclic citrullinated peptide positive) were identified. Recommended intakes of vegetables and fruits (>400 g/day) and red and processed meat (<500 g/week) were associated with lower risks of RA, with multivariable-adjusted odds ratios of 0.64 (95% CI 0.43-0.94) and 0.60 (95% CI 0.38-0.97), respectively. RCS revealed a positive linear association for total intake of red/processed meat with RA development and a negative association for vegetables and fruits. The risk was higher by quartile of red and processed meat intake for seropositive, but not seronegative RA.</p><p><strong>Conclusions: </strong>Higher intake of red/processed meat associated with a higher risk of seropositive RA, whereas vegetables and fruit may reduce the risk of RA overall.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616035","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":"When borders impact science: what is the future of European rheumatology research?","authors":"Frank Verhoeven, Athan Baillet, Celine Demougeot, Xavier Romand, Daniel Wendling, Axel Finckh, Francesco Ciccia, Rik Lories, Clement Prati","doi":"10.1016/j.ard.2025.06.2125","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2125","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607232","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":"Autoantibody reactome analysis reveals diagnostic biomarkers and molecular classification for relapsing polychondritis.","authors":"Yongmei Liu, Mengzhu Zhao, Lei Zhang, Jing Luo, Linlin Cheng, Haoting Zhan, Mansheng Li, Zijuan Zhang, Siyu Wang, Xinxin Feng, Min Feng, Haolong Li, Zhan Li, Jingdi Zhang, Yong Hou, Xiaobo Yu, Yongzhe Li","doi":"10.1016/j.ard.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.001","url":null,"abstract":"<p><strong>Objectives: </strong>The lack of effective biomarkers for relapsing polychondritis (RP) poses a significant challenge in its early diagnosis and treatment. This study aimed to identify novel autoantibodies and elucidate the pathogenesis and molecular heterogeneity of RP.</p><p><strong>Methods: </strong>Plasma samples from 467 RP patients, 164 healthy controls (HCs), and 186 disease controls (DCs) were analysed using 2 sequential microarrays and enzyme-linked immunosorbent assay to sequentially discover, validate, and verify new autoantibodies. Machine learning and differential analysis were used to identify diagnosis-specific autoantibodies and their correlation with disease activity, recurrence, and remission.</p><p><strong>Results: </strong>The RP group had 1344 elevated autoantibodies, discriminating RP patients from HCs. These antigenic targets were associated with pathways involving autoimmune responses, infections, and cardiovascular lesions. Two molecular subtypes characterised by distinct organ involvement and prognosis highlighted the heterogeneity of RP. Notably, 14 new autoantibodies were identified, which differentiated RP versus HCs and DCs with a sensitivity of 41% and 49.7% and a specificity of 91.7% and 90.5%, respectively. Among them, 6 autoantibodies showed better diagnostic performance and were consistently verified. Specifically, anti-C4B was positively correlated with disease activity, and increased anti-KRT16 predicted RP recurrence within 1 year. In addition, anti-C4B, anti-FNBP4, and anti-KRT10 decreased from acute attack to remission. Furthermore, the deposition of C4B protein in tracheal tissues, coupled with its reduction in plasma of RP patients, indicated that abnormal complement activation might be related to the pathological mechanism of RP.</p><p><strong>Conclusions: </strong>The 14 autoantibodies promoted a noninvasive early detection of RP, predicted disease recurrence and provided new insights into the understanding of RP pathogenesis.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599213","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":"Osteoarthritis risk associated with romosozumab compared with teriparatide in individuals with osteoporosis: a target trial emulation study.","authors":"Masaki Hatano, Yusuke Sasabuchi, Akira Okada, Yuya Kimura, Hisatoshi Ishikura, Takeyuki Tanaka, Taku Saito, Sakae Tanaka, Hideo Yasunaga","doi":"10.1016/j.ard.2025.06.2124","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2124","url":null,"abstract":"<p><strong>Objectives: </strong>To compare osteoarthritis among individuals with osteoporosis initiating romosozumab vs an active comparator.</p><p><strong>Methods: </strong>This new user comparative effectiveness study, emulating a target trial, included individuals aged ≥50 years in the administrative claims database from 2019 to 2022. Individuals who initiated romosozumab were compared with those who initiated teriparatide. The primary outcome was the incidence of osteoarthritis, while secondary outcomes included joint-specific osteoarthritis (knee, hip, and hand) at 1 year. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between romosozumab and teriparatide users, and inverse probability of censoring weighting (IPCW) was employed to account for informative censoring. Absolute risk reduction (ARR) and relative risk (RR) at 1 year were estimated using a weighted Kaplan-Meier estimator.</p><p><strong>Results: </strong>A total of 22,145 individuals were included in the study (87% female; mean age, 80 years). After IPTW-IPCW adjustment, romosozumab was associated with a lower risk of osteoarthritis compared with teriparatide (ARR, 1.1% [95% CI, 0.5%-1.8%]; RR, 0.79 [0.66, 0.89]). Joint-specific analyses showed the following results: knee osteoarthritis: ARR, 0.8% (95% CI, 0.3%-1.5%), RR, 0.79 (0.66, 0.92); hip osteoarthritis: ARR, 0.2% (95% CI, 0.0%-0.5%), RR, 0.68 (0.37, 1.05); and hand osteoarthritis: ARR, 0.2% (95% CI, 0.0%-0.4%), RR, 0.61 (0.35, 1.06).</p><p><strong>Conclusions: </strong>Romosozumab was associated with a lower risk of osteoarthritis than teriparatide among individuals with osteoporosis, particularly for knee osteoarthritis. Similar trends were observed for hip and hand osteoarthritis; however, the differences were not significant.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616034","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":"Development of an MHC imputation panel highlights independent contributions of HLA amino acid residues and C4 copy number variations to SLE risk.","authors":"Chae-Yeon Yu, Dong Mun Shin, Sung Min Kim, Yui Taek Lee, Sungwon Jeon, Sehwan Chun, So-Young Bang, Hye-Soon Lee, Xianyong Yin, Yong Cui, Xuejun Zhang, Jong Bhak, Soon Ji Yoo, Young Jin Kim, Bong-Jo Kim, Sang-Cheol Bae, Kwangwoo Kim","doi":"10.1016/j.ard.2025.06.2121","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2121","url":null,"abstract":"<p><strong>Objectives: </strong>Systemic lupus erythematosus (SLE) is a complex autoimmune disease strongly associated with the major histocompatibility complex (MHC) region, but precisely pinpointing the risk variants remains challenging. This study aimed to comprehensively profile SLE-driving variants using a newly developed East Asian MHC imputation reference panel, capable of simultaneously imputing diverse MHC variants, including multilevel human leukocyte antigen (HLA) variants and copy number variations (CNVs) of C4 elements, such as C4A, C4B, and human endogenous retrovirus (HERV).</p><p><strong>Methods: </strong>Using the whole-genome-sequencing (WGS) data from ∼2000 Korean samples, we genotyped and phased MHC variants, including HLA variants and C4-related CNVs, to construct an MHC reference panel. Imputation performance of the panel was assessed through leave-one-out cross-validation and validated using WGS and droplet digital polymerase chain reaction methodology. The panel was applied to 2 independent SLE genome-wide association study datasets, followed by stepwise conditional analyses, fine-mapping, and model comparisons.</p><p><strong>Results: </strong>The MHC panel achieved high imputation accuracies of 95% for HLA and 94% for C4 at the haploid-level. Independent contributions to SLE risk were identified from 6 amino acid positions altering the epitope-binding surfaces of HLA-DRB1 and HLA-C. Reduced C4A copy numbers and increased HERV copy numbers, collectively lowering C4 protein levels, were associated with increased SLE risk, independent of HLA variants. Our refined MHC-SLE association model provided superior explanations for SLE risk over previous association models in an independent Korean population.</p><p><strong>Conclusions: </strong>This study enhanced the understanding of HLA and C4 in SLE pathogenesis and holds promise for advancing MHC association studies for immune-mediated inflammatory disorders in East Asians using our MHC panel, accessible via https://coda.nih.go.kr/usab/kis/intro.do.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567010","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":"Highly selective tyrosine kinase 2 inhibition with zasocitinib (TAK-279) improves outcomes in patients with active psoriatic arthritis: a randomised phase 2b study.","authors":"Alan Kivitz, Xenofon Baraliakos, Elena Tomaselli Muensterman, Arthur Kavanaugh, Désirée van der Heijde, Piotr A Klimiuk, Guillermo Valenzuela, Eva Dokoupilova, Gabrielle Poirier, Bhaskar Srivastava, Sue Dasen, Xinyan Zhang, Ting Hong, Jingjing Chen, Peter Pothula, Haoling Holly Weng, Mona Trivedi, Apinya Lertratanakul","doi":"10.1016/j.ard.2025.05.023","DOIUrl":"https://doi.org/10.1016/j.ard.2025.05.023","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the efficacy, safety, and tolerability of the investigational, oral, allosteric, highly selective, and potent tyrosine kinase 2 inhibitor zasocitinib (TAK-279) in patients with active psoriatic arthritis (PsA).</p><p><strong>Methods: </strong>In this phase 2b, randomised, multicentre, double-blind, placebo-controlled, multiple-dose study, patients (≥18 years, with PsA symptoms for ≥6 months) received 30 mg, 15 mg, or 5 mg zasocitinib or placebo (1:1:1:1) once daily for 12 weeks, with a 4-week safety follow-up. The primary endpoint was American College of Rheumatology (ACR)20 response at week 12. Secondary efficacy endpoints included ACR50 response, ACR70 response, Psoriasis Area and Severity Index (PASI) 75 response among those with ≥3% body surface area at baseline and minimal disease activity (MDA) at week 12.</p><p><strong>Results: </strong>Overall, 290 patients (mean [SD] age, 49.9 [11.6] years; 57.2% female) received treatment. At week 12, 30 mg or 15 mg zasocitinib treatment resulted in significantly higher ACR20 responses (54.2%; P = .002 and 53.3%; P = .002, respectively) than placebo (29.2%). A numerically higher number of ACR50 responses were achieved at week 12 with 30 mg (26.4%; nominal P = .009) or 15 mg (26.7%; nominal P = .005) zasocitinib than placebo (9.7%). In addition, 30 mg zasocitinib demonstrated a numerically higher number of ACR70 responses (13.9% versus 5.6%, respectively; nominal P = .158), PASI 75 responses (45.7% versus 15.4%, respectively; nominal P = .002), and MDA (29.2% versus 12.5%, respectively; nominal P = .014) at week 12 versus placebo. In this small study of limited duration, most adverse events were mild/moderate and were more frequently observed in the higher dose group. In this small sample size, no new safety signals or clear dose-dependent laboratory parameter changes were identified.</p><p><strong>Conclusions: </strong>Here, 30 mg and 15 mg zasocitinib demonstrated efficacy across core domains in patients with active PsA with no new safety signals. These findings will be confirmed in ongoing larger studies of longer duration.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564310","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":"Spatially informed phenotyping by cyclic-in-situ-hybridisation identifies novel fibroblast populations and their pathogenic niches in systemic sclerosis.","authors":"Yi-Nan Li, Tim Filla, Andrea-Hermina Györfi, Minrui Liang, Veda Devakumar, Alexandru Micu, Hongtao Chai, Christina Bergmann, Ann-Christin Pecher, Jörg Henes, Pia Moinzadeh, Suzan Al-Gburi, Thomas Krieg, Alexander Kreuter, Jiucun Wang, Georg Schett, Bernhard Homey, Sascha Dietrich, Jörg H W Distler, Alexandru-Emil Matei","doi":"10.1016/j.ard.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.002","url":null,"abstract":"<p><strong>Objectives: </strong>Spatially nonresolved transcriptomic data identified several functionally distinct populations of fibroblasts in health and disease. However, in-depth transcriptional profiling in situ at the single-cell resolution has not been possible so far. We thus aimed to profile these populations by single-cell spatial transcriptomics using cyclic in situ hybridisation (cISH).</p><p><strong>Methods: </strong>We studied fibroblast subpopulations in the skin of systemic sclerosis (SSc) patients and heathy individuals using cISH as a novel approach for transcriptional phenotyping with subcellular resolution. Clustering was performed using Building Aggregates with a Neighbourhood Kernel and Spatial Yardstick (BANKSY) as a novel approach for spatially informed transcriptional phenotyping. The findings were further validated by integration with single-cell RNA sequencing in distinct SSc cohorts.</p><p><strong>Results: </strong>BANKSY-based spatially informed clustering identified 9 fibroblast (FB) subpopulations, with SFRP2+ reticular dermis (RetD) FB and CCL19+ nonperivascular (nonPV) FBs as novel subpopulations that reside in specific cellular niches and display unique gene expression profiles. SFRP2+ RetD FBs and CCL19+ nonPV FBs as well as COL8A1+ FBs display altered frequencies in SSc skin and play specific, disease-promoting roles for extracellular matrix release and leukocyte recruitment as revealed by their transcriptional profile, their cellular interactions, and ligand-receptor analyses. The frequencies of COL8A1+ FBs and their interactions with monocytic cells and B cells are associated with the progression of skin fibrosis in SSc.</p><p><strong>Conclusions: </strong>Our cISH-based, spatially resolved transcriptomic approach identified novel fibroblast subpopulations deregulated in SSc skin with specific pathogenic roles. COL8A1+ FBs and their immune interactions may also have potential as biomarkers for future progression of skin fibrosis.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551712","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":"Disease-modifying antirheumatic drug-free remission in psoriatic arthritis: is it attainable and sustainable? A large longitudinal study.","authors":"Selinde V J Snoeck Henkemans, Marijn Vis, Gonul Hazal Koc, Jolanda J Luime, Marc R Kok, Ilja Tchetverikov, Karen Visser, Lindy-Anne Korswagen, Jessica Bijsterbosch, Maikel van Oosterhout, Paul Baudoin, Jos H van der Kaap, Annette H M van der Helm-van Mil, Pascal H P de Jong","doi":"10.1016/j.ard.2025.04.022","DOIUrl":"10.1016/j.ard.2025.04.022","url":null,"abstract":"<p><strong>Objectives: </strong>According to current management guidelines for psoriatic arthritis (PsA) tapering of disease-modifying antirheumatic drugs (DMARDs) can be considered. However, limited data are available on complete DMARD cessation, also known as disease-modifying antirheumatic drug-free remission (DFR). Therefore, our aim was to investigate whether DFR is achievable and sustainable in PsA and to evaluate possible predictors for sustained disease-modifying antirheumatic drug-free remission (SDFR).</p><p><strong>Methods: </strong>From the Dutch southwest Early Psoriatic Arthritis cohort, all newly diagnosed patients with oligoarticular/polyarticular PsA who were treated with DMARDs were included (n = 451). Prevalence of (S)DFR and flare rates (early and late) were described. DFR was defined as the absence of clinical synovitis for ≥3 months after DMARD cessation, while for SDFR, a period of >1 year was used. Early and late flares were defined as restarting DMARD treatment ≤1 and >1 year after DMARD cessation, respectively. Subsequently, possible predictors for true SDFR, that is, SDFR without flaring were explored.</p><p><strong>Results: </strong>After a median of 5.1 years (IQR, 3.0-7.3 years), 22% of patients with PsA had reached DFR, and after reaching DFR, 4.7% had an early flare. Thus, SDFR was achieved in 14.4% of patients with PsA; 5.3% experienced a late flare, which occurred a median of 1.7 years (IQR, 1.4-2.8 years) after DMARD cessation. Eventually, 9.1% of patients reached true SDFR. Low baseline Disease Activity Index in Psoriatic Arthritis and never using biological or targeted synthetic DMARDs were independent predictors for true SDFR. At the time of true SDFR, the Health Assessment Questionnaire was similar to the general population (median, 0.12; IQR, 0-0.75).</p><p><strong>Conclusions: </strong>DFR is attainable in oligoarticular/polyarticular PsA and is sustainable in 9% of patients. However, the subgroup of patients with PsA with high disease activity at baseline and who require biological or targeted synthetic DMARDs do not achieve true SDFR. To our knowledge, this is the first study to demonstrate that chronicity can potentially be influenced in a proportion of patients with PsA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1130-1139"},"PeriodicalIF":20.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092342","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}