Annals of the Rheumatic Diseases最新文献

{"title":"Cigarette smoke-primed citrullinated HLA-DR4 T cell reactivity is modulated by γδ-T cells.","authors":"Matthias Jarlborg, Tine Decruy, Teddy Manuello, Julie Coudenys, Renée Van der Cruyssen, Thomas L A Malfait, Leander Meuris, Tania Maes, Ken R Bracke, Diane van der Woude, Aegli Athanasiadou, Ruth Wittoek, Peggy Jacques, Dirk Elewaut, Koen Venken","doi":"10.1016/j.ard.2025.10.031","DOIUrl":"10.1016/j.ard.2025.10.031","url":null,"abstract":"<p><strong>Objectives: </strong>Cigarette smoke (CS) increases the risk of seropositive rheumatoid arthritis (RA), particularly in individuals carrying HLA-DR4 (Human Leukocyte Antigen-DR4) shared epitope (SE) alleles, though the underlying mechanisms remain unclear. This study aimed to investigate the interaction between these 2 key risk factors-CS and HLA-DR4-and their effect on T cell responses to citrullinated antigens in early RA and in HLA-DR4 transgenic mice.</p><p><strong>Methods: </strong>Major histocompatibility complex (MHC)-II tetramer technology was used to detect CD4+ T cells specific for citrullinated antigens in patients with early SE+ RA and in HLA-DR4 transgenic mice. Mice were exposed to CS or immunised with citrullinated α-enolase (Cit-ENOL) to assess T cell responses. Systemic interleukin (IL)-23 overexpression was induced by hydrodynamic injection of IL-23-enhanced episomal vector.</p><p><strong>Results: </strong>CS exposure enhanced T cell reactivity to citrullinated peptides, including Cit-ENOL, in the lungs of both patients and mice. While Cit-ENOL T cells, either induced by CS or immunisation, did not directly trigger arthritis development, IL-23 overexpression unleashed their arthritogenic potential in immunised HLA-DR4 mice. Interestingly, CS exposure and Cit-ENOL immunisation led to γδ-T cell activation strongly correlating with Cit-ENOL T cell responses. Furthermore, γδ-T cell-deficient HLA-DR4 mice exhibited an aggravated arthritis phenotype, mirrored by altered functional Cit-ENOL T cell responses.</p><p><strong>Conclusions: </strong>These findings reveal a selective impact of CS on pulmonary T cell subsets and suggest that γδ T cells act as gatekeepers of HLA-DR4-mediated autoimmune responses in RA pathogenesis. They also highlight a potential 2-hit model involving IL-23 in driving T cell-mediated arthritis.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"730-742"},"PeriodicalIF":20.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595731","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":"Work smarter, not harder: achieve expert-level diagnosis extraction from medical records with optimal prompting of large language models.","authors":"Tjardo D Maarseveen, Daniyal Selani, Nils Steinz, Robin Ten Brinck, Herman K Glas, Josien Veris-van Dieren, Marcel J T Reinders, Erik B van den Akker, Rachel Knevel","doi":"10.1016/j.ard.2025.11.001","DOIUrl":"10.1016/j.ard.2025.11.001","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"778-780"},"PeriodicalIF":20.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628364","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":"Peripheral blood UBA1 variant burden predicts poor outcomes in VEXAS syndrome: a nationwide prospective study.","authors":"Yohei Kirino, Ayaka Maeda, Kana Higashitani, Nobuyuki Horita, Tomoyuki Asano, Kiyoshi Migita, Yoshikazu Motomura, Ryo Rokutanda, Daisuke Kobayashi, Masao Tamura, Nobuo Kanazawa, Kazunori Furuhashi, Yasushi Kondo, Ken Nagahata, Hiroki Takahashi, Hiroshi Kobayashi, Shuhei Yao, Keiko Yamagami, Kaori Uchino, Yukiko Hidaka, Hiroaki Ida, Dai Kishida, Tomohito Sato, Kunihiro Ichinose, Takako Miyamae, Kohei Tsujimoto, Yuta Inoue, Yuichiro Fujieda, Koji Mishima, Tomohiro Tsuji, Kazuki Tanaka, Haruka Noda, Shuntaro Isogai, Yuji Miyoshi, Naoto Yokogawa, Shinji Ota, Hirotake Sakuraba, Jumpei Nishi, Takuya Inoue, Sei Muraoka, Toshihiro Nanki, Toshimasa Shimizu, Tomohiro Koga, Yutaka Inaba, Masaki Matsubara, Kiyomi Yoshimoto, Anna Hasegawa, Kei Ikeda, Rena Motohashi, Yoichi Takeuchi, Motoaki Shiratsuchi, Masayori Moriyama, Kentaro Noda, Shinichiro Saito, Hiroyuki Hagiyama, Tetsuya Honda, Reiko Kageyama, Norie Nakatani, Tatsunori Goto, Mitsumasa Kishimoto, Tomoya Watanabe, Yukie Yamaguchi, Ryuta Nishikomori, Osamu Ohara, Tatsuma Ban, Tomohiko Tamura, Hideaki Nakajima","doi":"10.1016/j.ard.2026.03.003","DOIUrl":"https://doi.org/10.1016/j.ard.2026.03.003","url":null,"abstract":"<p><strong>Objectives: </strong>Vacuole, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome (VS) is a severe autoinflammatory disease caused by acquired pathogenic UBA1 variants and is associated with high mortality. This study aimed to identify predictors of poor outcomes in VEXAS syndrome.</p><p><strong>Methods: </strong>We conducted a nationwide prospective registry in Japan, in which all suspected cases underwent next-generation sequencing to detect pathogenic UBA1 variants and estimate the variant allele frequency (VAF) at baseline. Disease activity (VEXAS Current Activity Form [VEXASCAF]), serum C-reactive protein (CRP) level, prednisolone (PSL) dose, adverse events (AEs), mortality, and transfusion dependency were evaluated every 3 months for 1 year.</p><p><strong>Results: </strong>Among the screened patients, we included 60 patients with pathogenic UBA1 variants (all males; median age, 74 years) and 45 male patients with VS-like syndrome of similar age but without UBA1 variants served as controls. During a median follow-up of 343 days, the VEXASCAF and CRP levels decreased, whereas the PSL dose did not significantly change. Grade ≥3 AEs occurred in 50% of patients within 1 year. In the multivariable Cox regression analysis, a higher baseline VAF and higher PSL dose independently predicted poor prognosis, defined as death or transfusion dependence. The association between a higher VAF and poor outcomes was confirmed in 34 independent patients with VS. After adjusting for disease onset, patients carrying the UBA1 p.Met41Leu variant showed better survival. A similarly poor prognosis was observed in VEXAS-like patients.</p><p><strong>Conclusions: </strong>Baseline pathogenic UBA1 VAF serves as a potent prognostic biomarker for poor outcomes in VS and highlights its potential role in risk stratification.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607811","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":"Frequency and characteristics of axial involvement in psoriatic arthritis: results from the International Multicentre AXIS Study.","authors":"Murat Torgutalp, Raquel Almodovar, Valderilio F Azevedo, Xenofon Baraliakos, Filip Van den Bosch, Jürgen Braun, Vinod Chandran, Laura C Coates, Atul Deodhar, Torsten Diekhoff, Filippo Fagni, Alberto Floris, Floris A van Gaalen, Rodrigo Garcia-Salinas, Lianne S Gensler, Niti Goel, Alice B Gottlieb, Désirée van der Heijde, Philip S Helliwell, Kay Geert A Hermann, Umut Kalyoncu, Uta Kiltz, Francis Kynaston-Pearson, Robert Gw Lambert, Ramasharan Laxminarayan, Ying Ying Leung, Maria Llop, Clementina López-Medina, Alejandra López-Rodríguez, Michele M Luchetti Gentiloni, Miranda van Lunteren, Marina Magrey, Ajesh B Maharaj, Hernán Maldonado-Ficco, Walter P Maksymowych, Helena Marzo-Ortega, Marco Massarotti, Ashish J Mathew, Philip Mease, Peter Nash, Victoria Navarro-Compán, Mikkel Østergaard, Fabian Proft, Mikhail Protopopov, Roberto Ranza, Sherry Rohekar, Carlo Salvarani, Ruxandra E Schiotis, Nicholas Shenker, Joachim Sieper, Dilek Solmaz, Enrique R Soriano, Lai- Shan Tam, Ricardo Acayaba de Toledo, James Cc Wei, Nelly Ziade, Dafna D Gladman, Denis Poddubnyy","doi":"10.1016/j.ard.2026.02.025","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.025","url":null,"abstract":"<p><strong>Objectives: </strong>The Axial Involvement in Psoriatic Arthritis (AXIS) cohort aimed at evaluating the frequency of and clinical and imaging features of axial involvement in psoriatic arthritis (PsA).</p><p><strong>Methods: </strong>AXIS (NCT04434885) is a prospective, multicentre, cross-sectional study conducted in 19 countries, by the Assessment of SpondyloArthritis International Society and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Participants with a diagnosis of PsA meeting ClASsification criteria for Psoriatic ARthritis with musculoskeletal symptom duration ≤10 years and no prior exposure to biological or targeted synthetic disease-modifying antirheumatic drugs were consecutively included. Standardised clinical, laboratory, and imaging assessments (radiography and magnetic resonance imaging of the axial skeleton, including sacroiliac joints [SIJs] and spine), were performed. Imaging was reviewed locally and centrally to detect axial involvement. The presence of axial involvement was determined by local investigator judgement before and after central-imaging review.</p><p><strong>Results: </strong>Among 409 participants, axial involvement was identified in 153 (37.4%) based on the investigator's initial assessment and was decreased to 112 (27.4%) in the final evaluation after incorporating central-imaging review. Participants with axial involvement were younger (45.2 ± 13.8 vs 47.6 ± 12.6 years), more often male (56.3% vs 51.5%), and had a higher frequency of human leukocyte antigen (HLA)-B*27 positivity (22.4% vs 10.8%), inflammatory back pain (IBP) (74.7% vs 43.4%), and elevated C-reactive protein (CRP) (52.7% vs 37.4%). Active inflammatory and structural imaging changes were highly discriminative between participants with and without axial involvement. The central review identified imaging signs of axial involvement (active inflammation or structural lesions) in 95 participants (23.2%).</p><p><strong>Conclusions: </strong>Axial involvement was identified in 27.4% of participants with PsA after final diagnostic assessment, with associated features including HLA-B*27 positivity, IBP, elevated CRP, and imaging changes in SIJ or spine.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147525706","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":"EULAR recommendations for the management of Behçet's syndrome: 2025 update.","authors":"Gulen Hatemi, Sofia Ramiro, Yesim Ozguler, Sinem Nihal Esatoglu, Gunnar Tomasson, Stephane Barete, Alessandra Bettiol, Bahram Bodaghi, Vladimira Boyadzhieva, Luca Cantarini, Aykut Ferhat Celik, Omar Dhrif, Georgina Ducker, Giacomo Emmi, Ahmet Gül, Jörg Henes, Ina Koetter, Martin Krusche, Giuseppe Lopalco, Robert J Moots, David Saadoun, Carlo Salvarani, Petros Sfikakis, Aleksandra Stefanovic, Rosaria Talarico, Ilknur Tugal-Tutkun, Ugur Uygunoglu, Qianyu Zhao, Hasan Yazici","doi":"10.1016/j.ard.2026.02.009","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.009","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to update the European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of Behçet's syndrome according to the updated EULAR standard operating procedures.</p><p><strong>Methods: </strong>The task force comprised 29 members from 11 countries, including 19 rheumatologists, 2 ophthalmologists, 1 dermatologist, 1 gastroenterologist, 1 neurologist, 1 health professional, 2 patient research partners, and 2 Emerging EUlar NETwork members. Research questions were proposed by the task force through a Delphi survey and formulated into patients, interventions, comparison, and outcomes (PICO) questions for the systematic literature review. The results of the systematic literature review were discussed among the task force members. Previous recommendations and overarching principles were modified, and new recommendations were developed as needed. The updated recommendations were voted, and the levels of evidence and levels of agreement were determined.</p><p><strong>Results: </strong>The updated recommendations consist of 5 overarching principles and 12 recommendations that were tabulated according to organ involvement. Among the 12 recommendations, 1 was a new recommendation, 7 recommendations were modified, and only the wording was changed in 4 recommendations. The overarching principles focus on the importance of recognising the relapsing and remitting disease course and individualising treatment according to disease activity and prognostic risk factors, and emphasise the importance of a multidisciplinary approach, patient education, and shared decision making for optimal care. For mucocutaneous and joint involvement, colchicine is recommended as the first-line treatment modality. Apremilast and immunosuppressives such as tumour necrosis factor alpha (TNFα) inhibitors are recommended for refractory patients. For patients with organ involvement, more aggressive treatment with glucocorticoids and immunosuppressives is recommended for rapid induction of remission. Early use of monoclonal antibodies against TNFα is encouraged in patients with organ or life-threatening manifestations.</p><p><strong>Conclusions: </strong>These recommendations, which were updated based on new evidence and expert opinion, provide guidance for all stakeholders involved in the management of patients with Behçet's syndrome to improve the quality of care of these patients.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509028","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":"Human blood vessel organoids recapitulate key mechanisms of transition from vasculopathy to fibrosis in systemic sclerosis.","authors":"Yanhua Xiao, Xuezhi Hong, Langxian Zhi, Yi-Nan Li, Martin Regensburger, Franz Marxreiter, Boris Görg, Sarah Koziel, Andrea-Hermina Györfi, Tim Filla, Peter-Martin Bruch, Philipp Tripal, James Adjaye, Sascha Dietrich, Jürgen Winkler, Jörg H W Distler, Alexandru-Emil Matei","doi":"10.1016/j.ard.2026.02.021","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.021","url":null,"abstract":"<p><strong>Objectives: </strong>Systemic sclerosis (SSc) is an autoimmune disease that transitions from vasculopathy as an initiating pathogenic event to tissue fibrosis. The mechanisms of these transitions remain, however, poorly understood, mainly because complex multicellular human models of SSc vasculopathy are lacking. We aimed to develop a complex multicellular human model of SSc vasculopathy and use it to investigate the mechanisms underlying this process.</p><p><strong>Methods: </strong>Blood vessel organoids (BVOs) were derived from induced pluripotent stem cells of patients with SSc and healthy controls. Organoids were exposed to serum from patients with SSc with clinically manifest microvasculopathy or healthy donors. Structural and molecular changes were evaluated using confocal imaging, transcriptomic (RNA sequencing), epigenetic (assay for transposase-accessible chromatin sequencing), and spatial proteomic (codetection by indexing) profiling. Serum immunoglobulin G (IgG) was selectively depleted or enriched to investigate antibody contributions. Therapeutic interventions included bosentan and the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT).</p><p><strong>Results: </strong>SSc-derived BVOs exposed to SSc serum exhibited profound angiogenic defects, characterised by reduced vessel integrity, loss of endothelial-pericyte interactions, and induction of endothelial-to-mesenchymal transition (EndMT). Epigenetic and transcriptional profiling revealed upregulation of fibrosis-related genes and loss of endothelial markers. Spatial proteomic data confirmed EndMT at the protein level and demonstrated shifts in endothelial and pericyte subpopulation as well as alterations in their interactions reminiscent of those seen in tissues of patient with SSc. IgG depletion from SSc serum restored vascular structure, and transfer of SSc IgG to healthy serum phenocopied the pathological phenotype, implicating autoantibodies in endothelial injury. Both bosentan and DAPT partially reversed vascular abnormalities and downregulated EndMT markers.</p><p><strong>Conclusions: </strong>This study establishes BVOs as a complex human model of SSc vasculopathy and demonstrates in a multiomic approach that they recapitulate disease-specific vascular dysfunction and its transition to fibrosis. We show that genetic susceptibility and pathogenic autoantibodies synergise in driving microvascular injury in SSc. Furthermore, we provide evidence that SSc BVOs are a promising platform for evaluating therapies that prevent the transition from vasculopathy to fibrosis, and present Notch/γ-secretase inhibition as a potential novel target in SSc vasculopathy.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497426","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":"An immunometabolic signature of major depressive disorder in systemic lupus erythematosus.","authors":"Pierre Ellul, Nicolas Tchitchek, Grete Kvedaraviciute, Roberta Lorenzon, Isabelle Melki, Richard Delorme, Michelle Rosenzwajg, David Klatzmann","doi":"10.1016/j.ard.2026.02.019","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.019","url":null,"abstract":"<p><strong>Objectives: </strong>Systemic lupus erythematosus (SLE) frequently affects the central nervous system, leading to neuropsychiatric SLE (NPSLE). Major depressive disorder in SLE (SLE_MDD) is the most frequent manifestation of NPSLE and is believed to arise from an immune-mediated process. However, biomarkers for SLE_MDD remain lacking. The aim of this study was to identify candidate immunometabolic biomarkers associated with SLE_MDD.</p><p><strong>Methods: </strong>We analysed deep flow cytometry immune phenotyping, gut microbiota profiling, and targeted mass spectrometry-based metabolomics from 99 patients from the LUPIL-2 study (NCT02955615). Biological signatures were identified using unsupervised principal component analysis and supervised decision tree classification. They were then validated in an independent cohort from the TRANSIMMUNOM study (NCT02466217).</p><p><strong>Results: </strong>SLE_MDD patients exhibited a distinct immune profile with decreased naïve CD4⁺ T cells and naïve regulatory T cells (Tregs), alongside increased ICOS⁺ effector memory Tregs (94% classification accuracy). Gut microbiota diversity was reduced with depletion of Akkermansia muciniphila and enrichment of Faecalibacterium prausnitzii. Metabolomic analyses revealed disruptions in kynurenine and short-chain fatty acid pathways, including decreased butyrate levels. Integrative analyses demonstrated coordinated alterations linking Treg activation, microbial metabolites, and immune pathways, distinguishing SLE_MDD from SLE_non-MDD with up to 85% accuracy.</p><p><strong>Conclusions: </strong>SLE_MDD is associated with an immunometabolic signature involving alterations in Treg phenotype, gut microbiota composition, and metabolic pathways. These findings provide a rationale for future immunoregulatory or microbiota-targeted therapeutic strategies in SLE_MDD.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490439","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":"Inhibition of the type I interferon receptor pathway protects against muscle weakness induced by dermatomyositis serum.","authors":"Suchada Kaewin, Cecilia Leijding, Stefano Gastaldello, David Makari, Yi Zhong, Kristofer M Andreasson, Kent Jardemark, Maryam Dastmalchi, Begum Horuluoglu, Helene Alexanderson, Volker M Lauschke, Ingrid E Lundberg, Daniel C Andersson","doi":"10.1016/j.ard.2026.02.018","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.018","url":null,"abstract":"<p><strong>Objectives: </strong>Dermatomyositis (DM) is characterised by systemic inflammation, debilitating muscle weakness, cutaneous lesions, and increased mortality. An upregulation of type I interferon (IFN)-stimulated genes is observed in patients with DM. However, it remains unclear whether type I IFNs cause muscle weakness in DM. This study aimed to investigate the role of IFN-α/β receptor signalling in muscle weakness induced by factors in DM serum.</p><p><strong>Methods: </strong>In ex vivo experiments, flexor digitorum brevis muscles were isolated from healthy mice and incubated 24 hours with 10% healthy serum or serum from patients with DM (n = 9). To modulate IFN signalling, an antibody against the type I IFN receptor α/β subunit 1 (IFNAR1) or the Janus kinase-signal transducer and activator of transcription inhibitor ruxolitinib was used. RNA sequencing, followed by bioinformatics analysis, was conducted to identify differentially expressed genes and affected pathways related to IFN signalling.</p><p><strong>Results: </strong>Incubation with serum from patients with DM, but not that from healthy controls, caused significant muscle weakness manifested by a reduction in muscle force. Bioinformatic analyses revealed downregulation of type I IFN-inducible genes with IFNAR1 antibody. Pathway analysis showed enrichment of several IFN-related pathways. Inhibition of type I IFN signalling with either an IFNAR1 antibody or ruxolitinib abolished DM serum-induced effects.</p><p><strong>Conclusions: </strong>Factors in serum from patients with DM can activate the type I IFN signalling pathway in skeletal muscles, which constitutes an important causal factor for muscle weakness. Our data support a mechanistic model where blood-borne factors contribute to muscle disease phenotypes and underscore the therapeutic possibilities of pharmacological interventions targeting the IFNAR1 signalling pathway.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479488","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":"Neutrophil transcriptomics in SLE reveals intrinsic disease signatures, shared ex vivo adaptation, and transcriptional reset after CAR T-cell therapy.","authors":"Ehsan Dehdashtian, Guangnan Hu, Leah Whiteman, Md Tanimul Islam, Stefania Gallucci, Manuel Garber, Dominic Borie, Georg Schett, Roberto Caricchio","doi":"10.1016/j.ard.2026.02.013","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.013","url":null,"abstract":"<p><strong>Objectives: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by dysregulation of the adaptive and innate immunity. This study aimed to identify transcriptomic differences in neutrophils from patients with SLE and healthy individuals, analyse ex vivo adaptation dynamics, and evaluate the impact of chimeric antigen receptor (CAR) T-cell therapy on neutrophil transcriptomic profiles.</p><p><strong>Methods: </strong>Neutrophils were isolated via negative selection from 7 patients with SLE and 7 healthy individuals. RNA sequencing was performed to assess transcriptomic differences, ex vivo dynamics over 60 minutes, and responses to lipopolysaccharide (LPS) stimulation. In addition, longitudinal transcriptomic data from a patient with SLE undergoing KYV-101 anti-CD19 CAR T-cell therapy were evaluated.</p><p><strong>Results: </strong>We identified 258 differentially expressed genes consistently distinguishing SLE from healthy neutrophils; they spanned multiple clusters, enriched in interferon-related and DNA damage repair genes (upregulated), and ribosomal protein genes (downregulated). Ex vivo adaptation revealed shared activation pathways, such as NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and apoptosis, in both groups. LPS stimulation highlighted overlapping inflammatory responses, demonstrating retained functional capacities in SLE neutrophils. Following CAR T-cell therapy of a patient with SLE, neutrophil transcriptomic profiles were realigned with healthy controls by 3 months posttreatment.</p><p><strong>Conclusions: </strong>Neutrophils in SLE exhibit intrinsic, disease-specific transcriptomic alterations while sharing ex vivo adaptation dynamics with healthy individuals. The disease-specific alterations appear to be modifiable through targeted therapeutic intervention, as anti-CD19 CAR T-cell therapy resets neutrophil gene expression towards healthy patterns despite targeting B cells rather than neutrophils directly. These findings provide insights into SLE pathogenesis and highlight potential therapeutic strategies targeting both adaptive and innate immunity.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147479506","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":"Risk score for early mortality to stratify for intensive SSc therapy in the EUSTAR network: the RESIST score.","authors":"Ann-Christin Pecher, Marouane Boubaya, Yannick Allanore, Vanessa Smith, Jeska de Vries-Bouwstra, Radim Bečvář, Gianluca Moroncini, David Launay, Maria De Santis, Kamal Solanki, Carlomaurizio Montecucco, Luca Idolazzi, Fathi Nihal, Kotyla Przemyslaw, Marie-Elise Truchetet, Masataka Kuwana, Francesco Del Gado, Oliver Distler, Muriel Elhai, Jörg Henes","doi":"10.1016/j.ard.2026.01.016","DOIUrl":"https://doi.org/10.1016/j.ard.2026.01.016","url":null,"abstract":"<p><strong>Objectives: </strong>Systemic sclerosis (SSc) is associated with increased mortality. Intensive therapies have emerged for severe or refractory cases, but carry significant risks. The Risk score for Early mortality to Stratify for Intensive SSc Therapy (RESIST) score was developed to predict early mortality (<5 years) in patients eligible for such treatments.</p><p><strong>Methods: </strong>Using the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) cohort, patients unsuitable for intensive therapy were excluded. Survival was analysed via Kaplan-Meier estimates. A multivariable Cox model with adaptive LASSO (Least Absolute Shrinkage and Selection Operator) selection was built, informed by expert opinion, univariable analyses, and literature. Model performance was evaluated using the concordance index, area under the curve (AUC) at 3 and 5 years, and calibration. Missing data were imputed, and pseudo external validation was performed on 6251 excluded patients.</p><p><strong>Results: </strong>Of 22,059 EUSTAR patients, 4526 met the inclusion criteria; 138 died within 5 years. Deceased patients were more often male (28% vs 16%), older (53 vs 49 years), and had diffuse cutaneous SSc (dcSSc) (61% vs 35%) compared to survivors. The RESIST score included: male sex; dcSSc; age >55 years; elevated C-reactive protein; digital ulcers; modified Rodnan skin score >14; left ventricular ejection fraction <60%; and diffusing capacity of the lung for carbon monoxide <60%. This allowed patients with SSc to be discriminated into 3 groups with the following 5-year survival rates: low risk (99%, 95% CI: 98%-100%), intermediate risk (96%, 95% CI: 95%-97%), and high risk (82%, 95% CI: 78%-87%). The model showed good discrimination in both the development and validation cohorts (AUC: 0.79 [0.77-0.79] and 0.78 [0.77-0.79], respectively).</p><p><strong>Conclusions: </strong>The RESIST score reliably predicts early mortality in patients with SSc eligible for intensive therapies and may guide treatment decisions by identifying those at high risk of death.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472495","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}