Annals of the Rheumatic Diseases最新文献

{"title":"Discovery of tissue-specific proteomic signatures in juvenile dermatomyositis highlights pathways reflecting persistent disease activity, clinical heterogeneity, and myositis-specific autoantibody subtype.","authors":"Jessica Neely, Sara E Sabbagh, Jeffrey Dvergsten, Chioma Madubata, Celine C Berthier, Zilan Zheng, Christine Goudsmit, Sophia Matossian, Sean P Ferris, Gabriela K Fragiadakis, Marina Sirota, J Michelle Kahlenberg, Hanna Kim, Jessica L Turnier","doi":"10.1016/j.ard.2025.07.020","DOIUrl":"https://doi.org/10.1016/j.ard.2025.07.020","url":null,"abstract":"<p><strong>Objectives: </strong>Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune condition needing targeted treatment approaches and improved understanding of molecular mechanisms driving clinical phenotypes. We utilised exploratory proteomics from a longitudinal North American cohort of patients with new-onset JDM to identify biological pathways at disease onset and follow-up, tissue-specific disease activity, and myositis-specific autoantibody (MSA) status.</p><p><strong>Methods: </strong>We measured 3072 plasma proteins (Olink panel) in 56 patients with JDM within 12 weeks of starting treatment (from the Childhood Arthritis and Rheumatology Research Alliance Registry and 3 additional sites) and 8 paediatric controls. Twenty-four patients with JDM who had 6-month follow-up samples were assessed. We identified differentially expressed proteins (DEPs) between groups by fitting linear mixed effects models and associated DEPs with validated disease activity measures. We assessed for cell/tissue specificity using the Human Protein Atlas and JDM muscle single nuclei and skin single-cell transcriptomic datasets. Differences within MSA subgroups were also analysed.</p><p><strong>Results: </strong>We uncovered persistent dysregulation of innate immune activation, cell death, and redox signalling at 6 months despite multidrug immunosuppression. By leveraging tissue and cell-specific proteomes, we identified overrepresentation of circulating endothelial proteins associated with disease activity and verified endothelial cell marker expression in JDM muscle and skin. We discovered pathways associated with MSA subtypes that reflect JDM phenotypes. NXP2+ JDM-associated proteins reflected angiogenesis and extracellular matrix remodelling and were expressed in endothelial cells and fibroblasts. MDA5+ JDM was associated with circulating type III interferon and surfactant proteins.</p><p><strong>Conclusions: </strong>These proteomic findings will inform future biomarker and treatment development considering the unique tissue- and autoantibody-associated inflammation in JDM.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013667","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":"ASAS recommendations on reporting axial spondyloarthritis clinical trials.","authors":"Floris A van Gaalen, Victoria Navarro-Compán, Xenofon Baraliakos, Filip van den Bosch, Lianne S Gensler, Ihsane Hmamouchi, Robert Landewé, Pedro M Machado, Helena Marzo-Ortega, Valeria Rios Rodriguez, Denis Poddubnyy, Sofia Ramiro, Désirée van der Heijde","doi":"10.1016/j.ard.2025.07.017","DOIUrl":"https://doi.org/10.1016/j.ard.2025.07.017","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to develop recommendations on reporting baseline features and outcomes from axial spondyloarthritis (axSpA) clinical trials based on the recently updated instrument set of the Assessment of SpondyloArthritis international Society (ASAS) core outcome set (COS).</p><p><strong>Methods: </strong>A steering group (SG) convened a workgroup (WG), consisting of 13 ASAS members including rheumatologists, methodologists, epidemiologists, and 2 Young ASAS members. Recommendations on reporting axSpA trials baseline features and outcomes were developed in 3 steps: (1) the SG identified relevant baseline features from key axSpA clinical trials and formulated a proposal on how outcomes related to the instruments in the ASAS COS should be presented. (2) The SG proposal was presented, discussed, and modified in WG meetings. (3) WG proposal was discussed and voted on by ASAS members during the 2024 annual ASAS workshop.</p><p><strong>Results: </strong>Forty-two baseline features relevant for all axSpA clinical trials and 8 additional features for disease-modifying drug trials were defined including descriptions on how to report them. Additionally, recommendations on how to report 20 trial outcomes at baseline and follow-up timepoints were put forward. Finally, recommendations on how to report 11 outcomes of instruments additionally endorsed by ASAS but not in the COS were formulated. Proposals for baseline features, COS outcomes, and outcomes not in COS were approved by ASAS members (with 84%, 85%, and 93% of members in favour, respectively).</p><p><strong>Conclusions: </strong>These ASAS-endorsed recommendations on axSpA clinical trial reporting provide a standardised approach to reporting both baseline features as well as outcomes from axSpA clinical trials.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013693","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":"A germline IκBα mutation outside the signal reception domain blocks nuclear translocation of NFκB1 and associates with autoinflammation-like features.","authors":"Abdulwahab Elsayed, Ignatius Ryan Adriawan, Faranaz Atschekzei, Natalia Dubrowinskaja, Manfred Anim, Fabian Hauck, Ulrich Baumann, Torsten Witte, Georgios Sogkas","doi":"10.1016/j.ard.2025.08.010","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.010","url":null,"abstract":"<p><strong>Objectives: </strong>IκBα controls the canonical activation of NFκB. IκBα gain-of-function due to NFKBIA variants affecting the N-terminus of IκBα-especially residues 32 and 36-manifests with combined immunodeficiency. The role of NFKBIA variants affecting other IκBα domains has not been described.</p><p><strong>Methods: </strong>Variants in NFKBIA were identified using whole-exome sequencing. IκBα expression has been quantified by flow cytometry and Western blotting. Activation-induced IκBα degradation, NFκB1 activation, and nuclear translocation as well as inflammasome activity were evaluated.</p><p><strong>Results: </strong>The p.Gln228* variant in NFKBIA, identified in a family with a history of arthritis and psoriasis, did not affect induced degradation of IκBα. Its expression in HEK293T cells confirmed its truncating effect and revealed reduced NFκB activation. Similar to transfected HEK293T cells, peripheral blood mononuclear cells from patients harbouring the p.Gln228* variant displayed substantially reduced nuclear levels of NFκB1 p50. The latter findings suggest that the p.Gln228* variant causes a functional insufficiency of NFκB1. Similar to patients with NFκB1 haploinsufficiency, high serum levels of interleukin (IL)-18, as well as enhanced induced apoptosis-associated speck-like protein containing a caspase recruitment domain speck formation and IL-1β secretion in vitro, suggest enhanced inflammasome activation.</p><p><strong>Conclusions: </strong>NFKBIA variants not localising to the signal reception domain can affect IκBα function and consequently restrict the canonical activation of NFκB. In contrast to the phenotype of N-terminal variants, which is dominated by combined immunodeficiency, the here-reported C-terminal deletion of IκBα was identified in patients with autoinflammatory arthritis and psoriasis.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008081","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":"Evolution of osteitis condensans ilii-like sclerosis in first-time mothers by serial sacroiliac joint MRI during pregnancy and in the postpartum period.","authors":"Rosa Marie Kiil, Ulrich Weber, Anne Grethe Jurik","doi":"10.1016/j.ard.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.007","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to evaluate the evolution of subchondral sacroiliac joint (SIJ) sclerosis from pregnancy to 12 months postpartum, and to explore preceding and concomitant magnetic resonance imaging (MRI) features, potentially indicating osteitis condensans ilii (OCI).</p><p><strong>Methods: </strong>One hundred three first-time mothers were recruited for serial SIJ MRIs. MRI scans were performed at pregnancy weeks 20 and 32, and at 3, 6, and 12 months postpartum. Three readers independently evaluated subchondral sclerosis, bone marrow oedema (BME), fat lesions, and erosions. Sclerosis evolution and associations with BME, fat lesions, erosions, and pain were analysed.</p><p><strong>Results: </strong>The prevalence of iliac subchondral sclerosis increased gradually from 20% at pregnancy week 20% to 46% at 12 months postpartum, predominantly located in the upper-middle and anterior joint portions with depth expanding from a mean of 6.5 to 7.5 mm. BME and fat lesions were frequent with BME peaking at 3 months postpartum and fat lesions later in the postpartum period. Expanding depth of sclerosis at 12 months postpartum was associated with increasing prevalence of BME and fat lesions, but not with pain. At 12 months postpartum, BME and fat lesions meeting Assessment of SpondyloArthritis International Society thresholds were significantly more frequent with sclerosis ≥8 mm (50/40%) compared to sclerosis <8 mm (15/7%).</p><p><strong>Conclusions: </strong>Increasing depth of subchondral SIJ sclerosis during and after pregnancy was associated with BME peaking in the early and fat lesion in the late postpartum period suggesting that BME may precede the development of sclerosis and fat lesions. Sclerosis depth ≥8 mm, frequently accompanied by high-level BME and fat lesion, may serve as an MRI surrogate biomarker of radiographic OCI.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008013","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":"ERS/EULAR clinical practice guidelines for connective tissue diseases associated interstitial lung disease.","authors":"Katerina M Antoniou, Oliver Distler, Ana-Maria Gheorghiu, Catharina C Moor, Jens Vikse, Nikoleta Bizymi, Ilaria Galetti, Graham Brown, Elena Bargagli, Yannick Allanore, Tamera J Corte, Philippe Dieudé, Vincent Cottin, Benjamin A Fisher, Aurelie Fabre, Jon T Giles, Michael Kreuter, Ingrid E Lundberg, Venerino Poletti, Britta Maurer, Elisabetta A Renzoni, Ulf Müller-Ladner, Mary E Strek, Nicola Sverzellati, Paul Studenic, Jibril Mohammed, Blin Nagavci, Tanja Stamm, Thomy Tonia, Bruno Crestani, Anna-Maria Hoffmann-Vold","doi":"10.1016/j.ard.2025.08.021","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.021","url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung disease (ILD) is a frequent manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. Clinical practice guidelines to standardise screening, diagnosis, treatment and follow-up for CTD-ILD are of high importance for optimised patient care.</p><p><strong>Methods: </strong>A European Respiratory Society and European Alliance of Associations for Rheumatology task force committee, composed of pulmonologists, rheumatologists, pathologists, radiologists, methodologists and patient representatives, developed recommendations based on PICO (Patients, Intervention, Comparison, Outcomes) questions with grading of the evidence according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology and complementary narrative questions agreed on by both societies. For both PICO and narrative questions, the Evidence to Decision framework was used to formulate the recommendations.</p><p><strong>Results: </strong>The task force committee concluded with recommendations for 25 PICO and 28 narrative questions, regarding ILD in the context of systemic sclerosis, rheumatoid arthritis (RA), idiopathic inflammatory myopathies, Sjögren disease (SjD), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). In four narrative questions, regarding screening and assessment of risk for ILD progression in MCTD, SjD and SLE and one PICO question regarding pirfenidone in CTD-ILD other than RA-ILD, the task force had insufficient evidence to support recommendations. Screening, diagnostic, monitoring and treatment algorithms were developed based on the recommendations and usual clinical practice.</p><p><strong>Conclusions: </strong>We provide practical guidance by evidence-based recommendations to clinicians for each of the CTDs. In many cases there is low certainty or absence of evidence and we encourage further research to fill these gaps.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005893","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":"Identification of a novel transcriptome signature for predicting the response to anti-TNF-α treatment in patients with rheumatoid arthritis.","authors":"Lucia Santiago-Lamelas, Patricia Castro-Santos, Enrique J deAndrés-Galiana, Juan Luis Fernández-Martínez, Alejandro Escudero-Contreras, Carlos Pérez-Sanchez, Ismael Sánchez-Pareja, Chary López-Pedrera, Scott A Jelinsky, Maryia Nikitsina, Isidoro Gonzalez-Alvaro, Raquel Dos Santos Sobrín, Antonio Mera, Josefina Durán, Roberto Díaz-Peña","doi":"10.1016/j.ard.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.003","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to identify and validate a transcriptomic signature capable of predicting the response to tumour necrosis factor inhibitors (TNFi) therapy in patients with rheumatoid arthritis (RA) before treatment initiation.</p><p><strong>Methods: </strong>We performed a retrospective transcriptomic analysis using 2 public datasets, RNA-seq data from peripheral blood mononuclear cells (GSE138746) and microarray data from whole blood (GSE33377), to define a small-scale gene signature predictive of the response to TNFi treatment. Three external validations were then conducted, resulting in a total of 279 individuals, 169 responders, and 110 nonresponders.</p><p><strong>Results: </strong>Initial RNA-seq analysis (GSE138746) revealed 53 genes differentially expressed between responders and nonresponders; however, none of these genes remained significant after P value adjustment with the Benjamini-Hochberg method. A small-scale genetic signature comprising the 18 most discriminatory genes was then developed, achieving a leave-one-out cross-validation predictive accuracy of 88.75%. We further refined this list to 7 genes (COMTD1, MRPL24, DNTTIP1, GLS2, GTPBP2, IL18R1, and KCNK17) that effectively predicted the response to TNFi treatment, with an area under the receiver operating characteristic curve (AUC) of 0.84 in the GSE33377 dataset. Internal validation of the GSE138746 dataset yielded an AUC = 0.89. Finally, external validation confirmed the robustness of the 7-gene model (AUC ≥ 0.85).</p><p><strong>Conclusions: </strong>We identified a transcriptomic signature that aids the prediction of the response to TNFi treatment in patients with RA. These findings support its potential use as a precision medicine tool to improve therapeutic decision-making and reduce exposure to ineffective treatments in patients with RA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999507","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":"Satisfaction with telemedicine versus in-person visits in rheumatology: a noninferiority randomised controlled trial.","authors":"Lesley E Jackson, Jinoos Yazdany, Justin M Leach, Kenneth G Saag, Kiara Aaron, Jeffrey R Curtis, Sarah Goglin, Mary Margaretten, David H Chae, Diana Paez, Gary Cutter, Maria I Danila","doi":"10.1016/j.ard.2025.03.003","DOIUrl":"10.1016/j.ard.2025.03.003","url":null,"abstract":"<p><strong>Objectives: </strong>We tested whether a rheumatology telemedicine visit was noninferior to an in-person visit for patient satisfaction and care effectiveness, including for subgroups of age, sex, race and ethnicity, income, and employment status.</p><p><strong>Methods: </strong>This multicenter noninferiority trial randomised patients to 1 in-person or telemedicine visit. The primary outcome was the proportion of high visit satisfaction (9 or 10 on a 0-10 scale). The primary analysis tested whether patient satisfaction with telemedicine was noninferior to in-person care (10% noninferiority margin). Secondary and exploratory outcomes included preference for next visit type, satisfaction in subgroups, and immunosuppressant toxicity monitoring. We performed modified intent-to-treat (mITT) and per-protocol analyses.</p><p><strong>Results: </strong>Among 651 randomised patients (in-person, n = 323; telemedicine n = 328), 500 (76.8%) had a visit defining the mITT population. Satisfaction with telemedicine was not noninferior to in-person; 77.0% telemedicine, 90.1% in-person, difference 13.1% (90% CI, 7.7%-18.5%). Per-protocol analysis results were consistent. More participants in the in-person group compared with those in telemedicine preferred the same visit type for their next visit vs a different visit type/no preference (55.6% in-person, 19.1% telemedicine, P < .0001, mITT analysis). Men were equally satisfied with both visit types (90.0%), while women were more likely to be satisfied with in-person visits (90.2% vs 74.7%). Toxicity monitoring rates were higher in in-person vs telemedicine (eg, hepatic function: 92.1% vs 66.3%, P = .0001, per-protocol analysis).</p><p><strong>Conclusions: </strong>Among a large group of diverse patients, satisfaction with telemedicine was not noninferior to in-person rheumatology visits. More participants preferred in-person visits in the mITT and per-protocol analyses. Appropriate toxicity monitoring was lower in telemedicine vs in-person groups.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1591-1600"},"PeriodicalIF":20.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963885","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":"Antirheumatic drugs in reproduction, pregnancy, and lactation: a systematic literature review informing the 2024 update of the EULAR recommendations.","authors":"Andrea Pluma, Sabrina Hamroun, Linda Rüegg, Irene Cecchi, Malte Kramer, Luis Fernando Perez-Garcia, Tania Rivero, Axel Finckh, Yvette Meissner, Frauke Förger","doi":"10.1016/j.ard.2025.02.021","DOIUrl":"10.1016/j.ard.2025.02.021","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to summarise and update evidence to inform the 2024 update of the European Alliance of Associations for Rheumatology recommendations for the use of antirheumatic drugs in reproduction, pregnancy, and lactation.</p><p><strong>Methods: </strong>A systematic literature review (SLR) was performed, including keywords on reproduction, adverse pregnancy outcomes (APOs), and lactation. Two appraised SLRs were the basis for the SLR on drug safety in men. If sufficient data were available, a meta-analysis was performed on maternal drug exposure and the risk of APOs.</p><p><strong>Results: </strong>Of 6680 screened articles, 255 were included in the final analysis. In pregnancy, most evidence was available for biologic disease-modifying antirheumatic drugs (bDMARDs). Meta-analyses with adjusted risk estimates did not reveal APOs or serious infant infections to be associated with tumour necrosis factor inhibitor (TNFi) use. Data on non-TNFi bDMARDs did not raise concerns. In bDMARD-exposed infants, no serious adverse effects to rotavirus live vaccination were reported. Safety of Bacille Calmette-Guérin vaccination in TNFi-exposed infants could be a concern in the first 6 months of life. Regarding oral glucocorticoids, the SLR and meta-analysis using adjusted risk estimates found a dose-dependent association with an increased risk of preterm birth. Nonsteroidal anti-inflammatory drug use could reversibly reduce fecundability. Concerning lactation, available data on various bDMARDs was reassuring. In male patients, available evidence on methotrexate and most other drugs did not reveal adverse effects on sperm quality or birth outcomes. Cyclophosphamide remains the only drug that causes a dose-dependent irreversible infertility.</p><p><strong>Conclusions: </strong>This SLR provides up-to-date evidence to guide the 2024 update of the European Alliance of Associations for Rheumatology recommendations for the use of antirheumatic drugs in reproduction, pregnancy, and lactation.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1561-1590"},"PeriodicalIF":20.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960461","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":"Anti-TFAM antibodies link mitochondrial damage with antiphospholipid syndrome and thrombosis in SLE.","authors":"Eduardo Gómez-Bañuelos, Alessandra Ida Celia, Maria Isabel Trejo-Zambrano, Jesus Aureliano Robles-De Anda, Merlin Paz, Shruti Chaturvedi, Fabrizio Conti, Cristiano Alessandri, Eleni Tiniakou, Daniel W Goldman, Robert A Brodsky, Michelle Petri, Felipe Andrade","doi":"10.1016/j.ard.2025.04.015","DOIUrl":"10.1016/j.ard.2025.04.015","url":null,"abstract":"<p><strong>Objectives: </strong>Mitochondria are a source of autoantigens and damage-associated molecular patterns (DAMPs) in systemic lupus erythematosus (SLE). Nucleoids carrying TFAM (transcription factor A, mitochondrial) and mitochondrial DNA (mtDNA) are important DAMPs in SLE. While mtDNA has been associated with anti-double-stranded (ds)DNA antibodies and type I interferon (IFN-I), the immunogenic role of TFAM in SLE pathogenesis is unknown. Here, we characterised the clinical and transcriptional phenotypes linked to anti-TFAM antibodies in SLE.</p><p><strong>Methods: </strong>Anti-TFAM antibodies were discovered in an exploratory sample of 22 SLE patients and 9 healthy controls. To define the prevalence, clinical significance, and associations with transcriptional profiles and IFN levels, anti-TFAM antibodies were detected using enzyme-linked immunosorbent assay (ELISA) in 98 healthy controls and 158 SLE patients. Sera from patients with dermatomyositis, rheumatoid arthritis, and primary antiphospholipid syndrome (PAPS) were also tested.</p><p><strong>Results: </strong>Anti-TFAM antibodies were discovered in patients with SLE while analysing neutrophil autoantigens and confirmed by ELISA and immunoblotting. One-third of SLE patients (48/158) were positive for anti-TFAM antibodies. Unlike anti-dsDNA antibodies, anti-TFAM antibodies were not associated with disease activity or the IFN signature. Instead, anti-TFAM antibodies were associated with thrombosis, antiphospholipid syndrome (APS) (odds ratio [OR], 2.9 and 5.4, respectively), thrombosis-associated transcriptional profiles, and elevated IFN-III. Anti-TFAM antibodies were also found in PAPS, supporting their role in APS but not SLE pathogenesis. Lupus anticoagulant increased the risk of thrombosis associated with anti-TFAM antibodies (OR, 8.71), indicating they are markers of independent prothrombotic pathways.</p><p><strong>Conclusions: </strong>Anti-TFAM antibodies identify a distinct clinical and transcriptional disease subset associated with mitochondrial damage, thrombosis, and APS in SLE.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1501-1511"},"PeriodicalIF":20.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964753","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":"Anifrolumab in childhood-onset systemic lupus erythematosus: a promising option after belimumab failure.","authors":"Delia Argüelles Balas, Estefanía Barral Mena, Enrique Calvo-Aranda","doi":"10.1016/j.ard.2025.03.013","DOIUrl":"10.1016/j.ard.2025.03.013","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1608-1610"},"PeriodicalIF":20.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962078","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}