Annals of the Rheumatic Diseases最新文献

{"title":"Mitochondria-centred metabolomic map of inclusion body myositis: sex-specific alterations in central carbon metabolism.","authors":"Elie Naddaf, Ibrahim Shammas, Surendra Dasari, Xuan-Mai T Petterson, Wolfdieter Springer, Eugenia Trushina, Ian R Lanza","doi":"10.1016/j.ard.2025.05.003","DOIUrl":"10.1016/j.ard.2025.05.003","url":null,"abstract":"<p><strong>Objectives: </strong>To benchmark metabolomic signatures of inclusion body myositis (IBM) in muscle tissue, highlighting sex-specific differences and the correlation with clinical parameters.</p><p><strong>Methods: </strong>A total of 37 IBM patients and 22 controls without myopathy were included. All participants had bulk RNA sequencing performed previously. Clinical parameters included disease duration and manual muscle test (MMT) scores. Discovery metabolite screening and quantitative targeted metabolomics platforms were used. Levels of metabolites and RNA-metabolomic integrated modules were correlated with clinical parameters and the mitophagy marker, p-S65-Ubiquitin (p-S65-Ub).</p><p><strong>Results: </strong>IBM muscle samples showed elevated citric acid (TCA) cycle intermediates and anaplerotic amino acids. Proximal glycolytic intermediates were decreased, while pentose phosphate pathway (PPP) metabolites were increased. Short-chain acylcarnitines were lower in IBM males but not in females. Lastly, nucleic acid bases were increased, and nucleotides were decreased. MMT correlated with PPP metabolites and nucleic acid bases, and inversely correlated with glycolysis metabolites and mono/diphosphate nucleotides. MMT also correlated with several amino acids, including cysteine, taurine, carnosine, and sarcosine. Acylcarnitines correlated with disease duration only in males. Four RNA-metabolomic integrated modules demonstrated significant correlations. The strongest correlations were observed between the pink module and both sexes and p-S65-Ub. MMT and p-S65-Ub correlated with 3 and 2 modules, respectively. The enriched pathways were related to central carbon metabolism, cytokine/chemokine signalling, neurotransmission, and mitogen-activated protein kinase (MAPK)/RAS signalling. Males had relatively similar correlations to the combined-sex analysis, while females had no significant correlation with any module.</p><p><strong>Conclusions: </strong>IBM is associated with clinically significant alterations in central carbon metabolism, with the strongest RNA-metabolomic-clinical correlations observed in males. Further research is needed to explore the role of these metabolic changes in IBM pathogenesis and their progression over time.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1375-1386"},"PeriodicalIF":20.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224103","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":"Precision medicine and the chaos theory in rheumatoid arthritis.","authors":"Clément Triaille, Patrick Durez, Josef S Smolen, Iain B McInnes, Bernard Lauwerys, Nisha Limaye","doi":"10.1016/j.ard.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.ard.2025.07.005","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764416","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":"Efficacy of obinutuzumab in two rituximab refractory cases of idiopathic inflammatory myopathies with severe interstitial lung disease.","authors":"Ayla Nadja Stütz, Peter Kvacskay, Claus Peter Heußel, Nikolas Teichert, Hanns-Martin Lorenz, Jörg H W Distler, Johanna Mucke, Wolfgang Merkt","doi":"10.1016/j.ard.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.ard.2025.07.004","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758974","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 shared debt of art and rheumatology.","authors":"Alain Saraux, Dominique Le Nen","doi":"10.1016/j.ard.2025.07.012","DOIUrl":"https://doi.org/10.1016/j.ard.2025.07.012","url":null,"abstract":"<p><p>Medicine is not part of the fine arts. However, it is the art, scientifically informed, of care. Rheumatology in particular requires the ability to observe, listen, feel and interpret with humanity to care for people with musculoskeletal diseases. This narrative review explores the reciprocal links between art, artists, and musculoskeletal systems to seek to balance the debt of rheumatology to art with the debt of art to rheumatology over time. Before the Renaissance, knowledge about rheumatology was relatively poor and was largely restricted to Hippocratic theories and animal descriptions provided by Galen, and therefore poorly represented by artists. From 1480 to 1520, painters began to establish the field of artistic anatomy, focusing on the science of external forms. Although its impact on understanding rheumatic diseases was minimal, it led to the identification of anatomical structures affected by these conditions. Thus, human anatomy was born. After 1700, poor hygiene, a lack of physical activity, and overeating by the middle class were believed to be likely external causes of joint diseases, particularly gout, which was often conflated with other arthritis. Inspired by painters who idealised thermal baths, spas and seaside facilities were developed, promoting sports, hygiene, wellness, and healthy gastronomy. This gave birth to hydrotherapy. Patients with rheumatic diseases began congregating in balneological and thermal cities, allowing physicians to better describe the nosology of musculoskeletal diseases. Thus, rheumatology was born. More than 200 musculoskeletal conditions were documented between 1800 and 2000. Art and rheumatology share a debt, and rheumatologists began to engage with patients through art.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758976","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 glossary of signs and symptoms of giant cell arteritis.","authors":"Medha L Soowamber, Milena Bond, Zahi Touma, Carol Langford, Catalina Sanchez-Alvarez, Andy Abril, Sibel Zehra Aydin, Frank Buttgereit, Dario Camellino, Maria C Cid, Peter C Grayson, Bernhard Hellmich, William Lichliter, Tanaz A Kermani, Nader A Khalidi, Sarah L Mackie, Eric L Matteson, Mehrdad Maz, Peter A Merkel, Paul A Monach, Lorna Neill, Cristina Ponte, Carlo Salvarani, Wolfgang A Schmidt, Peter M Villiger, Kenneth J Warrington, Madeline Whitlock, Sofia Ramiro, Christian Dejaco","doi":"10.1016/j.ard.2025.06.2126","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2126","url":null,"abstract":"<p><strong>Objectives: </strong>This study seeks to create consensus-based definitions of signs and symptoms of giant cell arteritis (GCA) for use by health care professionals, primarily in research settings.</p><p><strong>Methods: </strong>Core definitions of signs and symptoms of GCA were extracted from 11 randomised controlled trials of GCA previously reviewed in a systematic literature review conducted in the context of the development of response criteria for GCA. This information was supplemented by definitions from other sources, such as rheumatology textbooks. A 2-round Delphi was performed within an international task force (32 members from 11 countries). The first round aimed to obtain consensus on the descriptive terms defining each sign or symptom, and round 2 rated the importance of these terms. Based on the Delphi study method, preliminary definitions were developed. In 4 online meetings, results of the Delphi were reviewed, and a consensus was achieved on final definitions.</p><p><strong>Results: </strong>Twenty-nine signs and symptoms of GCA were reviewed. Six signs or symptoms of GCA had previously been defined in the literature. A high level of agreement was reached on the definition of 23 signs and symptoms with the following 12 considered characteristic of GCA: headache, temporal artery abnormalities, scalp tenderness, scalp necrosis, jaw claudication, tongue claudication, tongue necrosis, amaurosis fugax, permanent vision loss, fever, limb claudication, and blood pressure inequality.</p><p><strong>Conclusions: </strong>A glossary of definitions for 23 signs and symptoms of GCA was developed through a consensus process involving international experts.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741020","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 case of systemic lupus erythematosus with favourable pregnancy outcome following continued administration of anifrolumab during pregnancy.","authors":"Ayako Kitada, Hiroto Tsuboi, Hiroshi Ebe, Saori Abe, Fumiyuki Shibasaki, Kotomi Murata, Moe Yamada, Mami Yoshida, Tomonori Hishinuma, Fumina Kawashima, Nana Uematsu, Toshiki Sugita, Masaru Shimizu, Ayako Ohyama, Hiromitsu Asashima, Haruka Miki, Yuya Kondo, Isao Matsumoto","doi":"10.1016/j.ard.2025.06.2135","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2135","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697484","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":"Differential molecular signatures in response to CD19-CAR T cell therapy compared with conventional pharmacotherapy in systemic lupus erythematosus.","authors":"Panagiotis Garantziotis, Lorenzo Beretta, Julius Lindblom, Georgia-Savina Moysidou, Dionysis Nikolopoulos, Ricardo Grieshaber-Bouyer, Melanie Hagen, Christina Bergmann, Andreas Wirsching, Aline Bozec, Matthias Schneider, Guillermo Barturen, George Bertsias, Dimitrios T Boumpas, Marta E Alarcón-Riquelme, Andreas Mackensen, Georg Schett, Ioannis Parodis","doi":"10.1016/j.ard.2025.06.2132","DOIUrl":"https://doi.org/10.1016/j.ard.2025.06.2132","url":null,"abstract":"<p><strong>Objectives: </strong>Early trials of CD19-chimeric antigen receptor (CAR) T cell therapy in systemic lupus erythematosus (SLE) show promise, but the molecular mechanisms underlying its disease-modifying effects remain unclear. We aimed to compare biological profiles and alterations following CD19-CAR T cell versus standard pharmacotherapy in SLE.</p><p><strong>Methods: </strong>Pseudo-bulk gene expression derived from single-cell RNA sequencing of peripheral blood mononuclear cells from 7 SLE patients before and after CD19-CAR T cell therapy was compared with whole-blood transcriptome data from 30 SLE patients in remission on standard pharmacotherapy and 31 SLE patients before and 6 months after treatment with rituximab, belimumab, or cyclophosphamide. Pathway analysis was conducted using Functional Analysis of Individual Microarray Expression and gene set enrichment analysis.</p><p><strong>Results: </strong>CD19-CAR T cell-induced remission was characterised by marked suppression of complement activation, type I interferon, DNA damage response (DDR), and cell death pathways compared with remission following conventional pharmacotherapy, alongside an upregulation of lipid metabolism pathways. Compared with rituximab and belimumab, CD19-CAR T cell therapy induced greater downregulation of type I/II interferon, DDR, and chemokine pathways. Compared with cyclophosphamide, CD19-CAR T cell therapy induced greater suppression of interferon, mitochondrial, and mammalian target of rapamycin signalling pathways.</p><p><strong>Conclusions: </strong>CD19-CAR T cell therapy induces substantial suppression of key immunological pathways involved in SLE, including complement activation and type I interferon responses, accompanied by a metabolic reprogramming. Molecular profiles of remission after CD19-CAR T cell therapy differ from those induced by conventional SLE pharmacotherapy, suggesting more profound CD19-CAR T cell-induced biological alterations.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697485","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":"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":"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}