Lancet Rheumatology最新文献

{"title":"Towards precision medicine in antiphospholipid syndrome.","authors":"Chary Lopez-Pedrera, Carlos Pérez-Sánchez, Maria G Tektonidou","doi":"10.1016/S2665-9913(25)00094-3","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00094-3","url":null,"abstract":"<p><p>Antiphospholipid syndrome is a rare systemic autoimmune disorder with complex pathophysiology and high heterogeneity in clinical presentation and treatment responses. The core idea of precision medicine is that the varying treatment responses among patients with the same clinical diagnosis are due to differences in their underlying pathogenetic mechanisms and genetic makeup. A better understanding of the pathophysiology and multiple clinical subtypes of antiphospholipid syndrome has led to better classification and subphenotyping of the syndrome. Advances in microarray analysis, cytometry, and omic technologies have helped to identify genes, epigenetic variations, and pathway-informed biomarkers and identified new factors in disease development. By stratifying patients with antiphospholipid syndrome based on clinical or laboratory phenotypes and cellular and molecular profiles in the blood and affected tissues, treatments can be more effectively tailored, improving efficacy and reducing toxicity. This Review explores the current evidence on clinical, genetic, and biomolecular stratification in antiphospholipid syndrome and how artificial intelligence algorithms from clinical and molecular profiles can guide precision medicine in antiphospholipid syndrome.</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144152234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One step closer to predicting autoimmune congenital heart block?","authors":"Grégoire Martin de Frémont, Nathalie Morel, Nathalie Costedoat-Chalumeau","doi":"10.1016/S2665-9913(25)00129-8","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00129-8","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144072","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":"Treatment outcomes in patients with VEXAS syndrome: a retrospective cohort study.","authors":"Adam Al-Hakim, Roochi Trikha, Ei Ei Phyu Htut, Onima Chowdhury, Calman A MacLennan, Ashlyn Chee, Arvind Kaul, James A Poulter, Catherine Cargo, James M S Wason, Sammiya Ahmed, Tanya N Basu, Sukanya Gogoi, James Galloway, Stephen Jolles, Anoop Mistry, Elspeth M Payne, Rachel S Tattersall, Taryn Youngstein, Helen J Lachmann, Austin Kulasekararaj, Sinisa Savic","doi":"10.1016/S2665-9913(25)00034-7","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00034-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently described autoinflammatory disorder with little therapeutic evidence. We compared treatment outcomes of targeted therapies versus prednisolone alone in the largest UK cohort of patients with VEXAS syndrome to date.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this retrospective cohort study, we analysed the outcomes of targeted therapies in patients with VEXAS syndrome in six tertiary referral centres across the UK between July 22, 2014, and Oct 19, 2024. The inclusion criteria were genetically confirmed VEXAS syndrome and receipt of at least one targeted therapy or prednisolone alone. Patients without clinical information at all timepoints after baseline were excluded. Data collection forms were used to record clinical and biochemical data at the following timepoints: time of diagnosis, initiation of treatment, and follow-up at 3 months, 6 months, and 12 months from the initiation of treatment (±28 days). Laboratory parameters, including C-reactive protein (CRP) and haemoglobin, and glucocorticoid doses were collected at each timepoint and compared between timepoints. Primary outcomes were complete response (ie, clinical remission, CRP ≤10 mg/L, and prednisolone ≤10 mg per day) and partial response (ie, clinical remission with ≥50% reductions in both CRP and glucocorticoid dose from baseline) to treatment. Treatment discontinuation and adverse events were documented for each treatment. Due to the high prevalence of cytopenias in VEXAS syndrome, these were only recorded as adverse events when necessitating treatment change. People with lived experience were not involved in the study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;We analysed 71 targeted therapies in 59 patients with genetically confirmed VEXAS syndrome. Of the 59 patients, 58 (98%) were male and one (2%) was female, with a mean age of 71 years (SD 8), and 27 (46%) had myelodysplastic syndrome. The treatments included tocilizumab (n=19), anakinra (n=13), azacitidine (n=13), baricitinib (n=11), and prednisolone only (n=10). At 6 months, in those who continued therapy, ten (91%) of 11 patients receiving azacitidine showed a response (three [27%] complete responses), as well as did seven (64%) of 11 receiving tocilizumab (four [36%] complete responses), three (100%) of three receiving anakinra (one [33%] complete response), and two (40%) of five receiving baricitinib (no complete responses). Although all patients who tolerated anakinra had a response, the discontinuation rate was high (eight [62%] of 13), mostly due to severe injection-site reactions (n=5). Patients were more likely to respond to azacitidine than to other therapies at 6 months (risk ratio 2·47, 95% CI 1·18-5·20; p=0·018). Absence of fever or thromboembolism at diagnosis was associated with better outcomes. By 6 months, median CRP concentrations had decreased in patients receiving tocilizumab (from 30 mg/L [IQR 13-45] to 4 ","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144074","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":"Maternal autoantibodies to the sodium potassium pump α1 subunit AT1A1 and fetal autoimmune congenital heart block: a case-control study.","authors":"Stephanie Benjamin, Lisa Vi, Diptendu Chatterjee, Edgar T Jaeggi, Amelia Ruffatti, Linda T Hiraki, Lusia Sepiashvili, Carl A Laskin, Meena Fatah, Marta Tonello, Daniela Dominguez, Lawrence Ng, Michelle Lohbihler, Andre D Luchessi, Kaley Hogarth, Abdelkader Daoud, Jason T Maynes, Stephanie Protze, Robert M Hamilton","doi":"10.1016/S2665-9913(25)00092-X","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00092-X","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Fetal autoimmune congenital heart block is a rare but life-threatening condition that is difficult to predict. This study sought to identify a serological biomarker predictive of autoimmune congenital heart block in pregnancies at risk due to maternal systemic lupus erythematosus, Sjögren's disease, undifferentiated connective tissue disease, or a history of congenital heart block offspring.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This case-control study analysed maternal blood samples from pregnancies affected and unaffected by autoimmune congenital heart block from two centres (The Hospital for Sick Children, Canada, and The University of Padua, Italy). Serum samples collected across varying gestational ages were used for biomarker discovery, verification, and validation. The key inclusion criterion was a positive clinical test for maternal anti-Sjögren's syndrome-related antigen A/Ro autoantibodies, and the key exclusion criterion was structural congenital heart disease associated with heart block. Cases were pregnancies that resulted in fetal or neonatal congenital heart block and controls were pregnancies that resulted in offspring with a normal heart rhythm. Two-dimensional western blotting was used to identify maternal autoantibodies targeting fetal cardiac proteins, using fetal heart tissue and stem-cell-derived cardiomyocytes. Findings were validated using commercial proteins. Sensitivity and specificity for predicting fetal heart block outcomes were assessed using receiver-operating characteristic curves. The primary study outcomes were the presence and specificity of anti-cardiac autoantibodies in autoimmune congenital heart block cases versus controls, the association between specific autoantibodies and congenital heart block development, and the predictive accuracy of identified autoantibodies. This study did not involve individuals with lived experience in the study design or implementation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Serum samples were collected between Jan 1, 2010, and Dec 31, 2020, in the discovery cohort (The Hospital for Sick Children), between Aug 1, 1999, and Dec 31, 2019 in the verification cohort (University Hospital of Padua), and between June 1, 2018, and Aug 31, 2023, in the validation cohort (The Hospital for Sick Children). Mean maternal age was 34·2 years (SD 5·2) in the discovery cohort, 33·5 years (4·6) in the verification cohort, and 32·8 years (4·3) in the validation cohort. Maternal serum samples from pregnancies affected by fetal autoimmune congenital heart block (cases; n=46) showed an expanded repertoire of anti-cardiac autoantibodies compared with unaffected pregnancies (controls; n=65). Mass spectrometry identified 11 potential cardiac protein targets for maternal autoantibodies and the presence of seven autoantibodies were confirmed in serum samples from affected pregnancies. Four targets were identified before the onset of congenital heart block (ANXA1, BIP, MYPC3, and AT1A1).","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144071","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":"Treatment outcomes in VEXAS syndrome: response is in the eye of the definer.","authors":"Matthew Koster","doi":"10.1016/S2665-9913(25)00074-8","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00074-8","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144076","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":"IgG4-related disease: the future is promising","authors":"The Lancet Rheumatology","doi":"10.1016/S2665-9913(25)00134-1","DOIUrl":"10.1016/S2665-9913(25)00134-1","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 6","pages":"Page e377"},"PeriodicalIF":15.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089676","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":"Research in Brief","authors":"Jennifer Thorley","doi":"10.1016/S2665-9913(25)00133-X","DOIUrl":"10.1016/S2665-9913(25)00133-X","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 6","pages":"Page e387"},"PeriodicalIF":15.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089677","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 imaging crisis in axial spondyloarthritis.","authors":"Torsten Diekhoff, Denis Poddubnyy","doi":"10.1016/S2665-9913(25)00108-0","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00108-0","url":null,"abstract":"<p><p>Imaging holds a pivotal yet contentious role in the early diagnosis of axial spondyloarthritis. Although MRI has enhanced our ability to detect early inflammatory changes, particularly bone marrow oedema in the sacroiliac joints, the poor specificity of this finding introduces a substantial risk of overdiagnosis. The well intentioned push by rheumatologists towards earlier intervention could inadvertently lead to the misclassification of mechanical or degenerative conditions (eg, osteitis condensans ilii) as inflammatory disease, especially in the absence of structural lesions. Diagnostic uncertainty is further fuelled by anatomical variability, sex differences, and suboptimal imaging protocols. Current strategies-such as quantifying bone marrow oedema and analysing its distribution patterns, and integrating clinical and laboratory data-offer partial guidance for avoiding overdiagnosis but fall short of resolving the core diagnostic dilemma. Emerging imaging technologies, including high-resolution sequences, quantitative MRI, radiomics, and artificial intelligence, could improve diagnostic precision, but these tools remain exploratory. This Viewpoint underscores the need for a shift in imaging approaches, recognising that although timely diagnosis and treatment is essential to prevent long-term structural damage, robust and reliable imaging criteria are also needed. Without such advances, the imaging field risks repeating past missteps seen in other rheumatological conditions.</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102959","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":"Predicting the risk of subsequent progression in patients with systemic sclerosis-associated interstitial lung disease with progression: a multicentre observational cohort study.","authors":"Anna-Maria Hoffmann-Vold, Liubov Petelytska, Håvard Fretheim, Trond Mogens Aaløkken, Mike Oliver Becker, Hilde Jenssen Bjørkekjær, Cathrine Brunborg, Cosimo Bruni, Christian Clarenbach, Phuong Phuong Diep, Rucsandra Dobrota, Michael T Durheim, Muriel Elhai, Thomas Frauenfelder, Suiyuan Huang, Suzana Jordan, Emily Langballe, Øyvind Midtvedt, Carina Mihai, Erica Mulcaire-Jones, Janelle Vu Pugashetti, Marco Sprecher, Justin Oldham, Øyvind Molberg, Dinesh Khanna, Oliver Distler","doi":"10.1016/S2665-9913(25)00026-8","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00026-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;In patients with systemic sclerosis, it is common practice to treat interstitial lung disease (ILD) in patients in whom progression has already occurred. We sought to clarify whether observed progression of systemic sclerosis-associated ILD confers risk for subsequent progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this multicentre observational cohort study, based on an analysis of prospectively collected data, we included patients with systemic sclerosis-associated ILD aged 18 years or older at diagnosis, who fulfilled the 2013 American College of Rheumatology-European Association of Alliances in Rheumatology systemic sclerosis classification criteria. The main cohort (diagnosed between January 2001 and December 2019) was consecutively followed up annually over 4 years at the Department of Rheumatology at the Oslo University Hospital, Norway, and the Department of Rheumatology at the University Hospital Zurich, Switzerland. We applied four definitions of ILD progression: the primary definition was forced vital capacity (FVC) decline of 5% or more, and secondary definitions included FVC decline of 10% or more, progressive pulmonary fibrosis (PPF), and progressive fibrosing ILD (PF-ILD). We applied these definitions at each annual visit after the first (visit 1). We validated our findings in an enriched cohort that included patients from the main cohort with systemic sclerosis-associated ILD and short disease duration of less than 3 years along with patients diagnosed between January 2003 and September 2019 from the Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA. Multivariable logistic regression analyses were applied to predict ILD progression and its effect on mortality. There was no involvement of people with lived experience in this study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Of 231 patients with systemic sclerosis-associated ILD from the main cohort (mean age 48·0 years [SD 14·6], 176 [76%] female and 55 [24%] male), 71 (31%) had ILD progression as defined by an FVC decline of 5% or more between visit 1 and visit 2, 38 (16%) as defined by an FVC decline of 10% or more, 39 (17%) as defined by PPF, and 89 (39%) defined by PF-ILD. In multivariable logistic regression analyses, adjusted for risk factors for progressive systemic sclerosis-associated ILD and immunosuppressive treatment, we found that ILD progression, defined by FVC decline of 5% or more, from visit 1 to visit 2 reduced the risk for further progression from visit 2 to visit 3 (odds ratio [OR] 0·28 [95% CI 0·12-0·63]; p=0·002) and that there was no risk for subsequent progression using the other definitions (FVC decline of ≥10%: 0·57 [0·16-1·99; p=0·38]; PPF: 0·93 [0·39-2·22; p=0·88]; and PF-ILD: 0·69 [0·35-1·36]; p=0·28]). Using the primary definition of progression, we found the same results in the enriched systemic sclerosis-associated ILD cohort, wherein 41 (34%) of 121 patients had progression defined by an FVC decline of 5% or ","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095802","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":"Why is progressive ILD in systemic sclerosis so difficult to predict?","authors":"Kathleen Morrisroe, Murray Barron","doi":"10.1016/S2665-9913(25)00068-2","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00068-2","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095805","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}