RMD Open最新文献

{"title":"Systemic lupus erythematosus damage risk index (SLE-DRI): a simple machine learning-based tool for identifying patients at risk for early organ damage.","authors":"Panagiotis Garantziotis, Dionysis Nikolopoulos, Spyridon Katechis, Alp Temiz, Danae-Mona Nöthling, Christina Adamichou, Christina Bergmann, Prodromos Sidiropoulos, Georg Schett, Antonis Fanouriakis, Dimitrios T Boumpas, George Bertsias","doi":"10.1136/rmdopen-2025-006009","DOIUrl":"https://doi.org/10.1136/rmdopen-2025-006009","url":null,"abstract":"<p><strong>Objective: </strong>Organ damage is a key determinant of poor prognosis and increased mortality in systemic lupus erythematosus (SLE). However, no validated clinical tools for predicting damage accumulation currently exist. We sought to develop a machine learning-based model to predict early organ damage in patients with SLE.</p><p><strong>Methods: </strong>Classification criteria (American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, European League Against Rheumatism (EULAR)/ACR-2019) and non-criteria features of a cohort of 914 patients with SLE were analysed to predict damage (defined as SLICC/ACR Damage Index (SDI)) within 5 years since diagnosis. Feature selection and model construction were performed using the least absolute shrinkage and selection operator-logistic regression (LASSO-LR). The best model in 10-fold cross-validation was tested in an external cohort (n=50).</p><p><strong>Results: </strong>A LASSO-LR model incorporating 16 criteria and non-criteria features predicted early organ damage with area under the receiver operating characteristic curve (AUC) values of 0.80 (95% CI 0.74 to 0.87) and 0.86 (95% CI 0.76 to 0.97) in the derivation and external validation cohorts, respectively, outperforming the ACR-1997 (AUC 0.70; 95% CI 0.62 to 0.78), SLICC-2012 (AUC 0.74; 95% CI 0.66 to 0.81) and EULAR/ACR-2019 (AUC 0.70; 95% CI 0.63 to 0.78) classification systems. Features most strongly associated with damage included the SLICC-2012 neurological disorder, EULAR/ACR-2019 class III/IV lupus nephritis and among non-criteria manifestations, myocarditis and interstitial lung disease. Operating the model as a binary classifier (early damage versus no damage), it demonstrated high specificity (0.90, 95% CI 0.78 to 0.95). The model can be converted to a simplified scoring system, with a threshold of ≥3 achieving an AUC of 0.86 (95% CI 0.75 to 0.96).</p><p><strong>Conclusion: </strong>We developed and validated a clinician-friendly model for early organ damage prediction in SLE, facilitating risk stratification.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intra-articular sustained-release colchicine is efficacious in an inflammatory arthritis rat model.","authors":"Julien Grassot, Farah Marzouki, Roxane Hervé, Magali Breckler, Luca Semerano, Natacha Bessis, Hang-Korng Ea, Charles Sanson, Gauthier Pouliquen, Philippe Pouletty, Marie-Christophe Boissier, Elodie Rivière","doi":"10.1136/rmdopen-2025-005988","DOIUrl":"10.1136/rmdopen-2025-005988","url":null,"abstract":"<p><strong>Objectives: </strong>Gout is a common disease causing excruciatingly painful and disabling flares. Although currently approved treatments for gout flares are generally effective, their use is restricted in many patients who present contraindications. There is a clear unmet need for treatments, with a rapid onset of action and a good safety profile. This study evaluates the efficacy of intra-articular (IA) colchicine (COL)-loaded microspheres enabling sustained-release colchicine (SR-COL), and of a combination of SR-COL with an anaesthetic (Ropivacaine HCl, ROPI) (PKM-01) in a rat model of acute inflammatory arthritis.</p><p><strong>Methods: </strong>PKM-01 combines ROPI with SR-COL, prepared using a polylactic-co-glycolic acid matrix polymer. A model of IA carrageenan (CAR)-induced arthritis in knees or ankles was adapted for this study. Treatments (phosphate buffer saline, dexamethasone, SR-COL, ROPI or PKM-01) were administered intra-articularly immediately following the CAR injection. Pain was assessed using Von Frey filaments or weight-bearing tests. Histological scores assessed joint inflammation and destruction.</p><p><strong>Results: </strong>All animals experienced acute painful and destructive arthritis following CAR injection. ROPI effectively alleviated pain but had no significant impact on inflammation or joint destruction. SR-COL demonstrated efficacy in reducing pain, inflammation and joint destruction across all parameters. PKM-01 provided a strong and rapid analgesic effect and exhibited anti-inflammatory properties, as evidenced by histological analysis of joint inflammation and destruction. Blood levels of COL after ankle injections were significantly below toxicity thresholds.</p><p><strong>Conclusions: </strong>These data indicate that PKM-01 may serve as an effective and safe treatment option for acute inflammatory arthritis. A clinical trial is planned in gout flare patients.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between metabolic conditions, physical activity and self-efficacy before and after a first-line exercise and education intervention for osteoarthritis: a longitudinal register study using the SOAD cohort.","authors":"Filippo Recenti, Simone Battista, Stefan Lohmander, Johanna Vinblad, Ali Kiadaliri, Allan Abbott, Ola Rolfson, Martin Englund, Marco Testa, Andrea Dell'Isola","doi":"10.1136/rmdopen-2025-005804","DOIUrl":"10.1136/rmdopen-2025-005804","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the association of diabetes, hypertension and overweight/obesity with physical activity (PA), self-efficacy for pain and self-efficacy for other symptoms before and after a 6- week exercise and education intervention for knee and hip osteoarthritis (OA), and to assess outcome disparities based on metabolic health.</p><p><strong>Methods: </strong>Register-based cohort study using the Swedish Osteoarthritis and Diabetes cohort. We used Body Mass Index, medical records and medication dispensation to define overweight/obesity, hypertension and diabetes at baseline (exposures). PA was self-reported (weekly minutes), and self-efficacy was measured using the 'Arthritis Self-Efficacy Scale' (ASES) (score 10-100) (outcomes). We used linear mixed-effect models to estimate associations between exposures and outcomes, adjusted for confounders.</p><p><strong>Results: </strong>We included 80 893 individuals with knee or hip OA. Those with metabolic conditions consistently showed lower PA and self-efficacy, with baseline disparities persisting after the intervention, particularly when all three conditions coexisted (PA difference: baseline 107 min [95% CI: 97; 118], 3-month 97 [86; 108], 12-month 109 [95; 123]; ASES-pain difference: baseline 5.6 [3.9; 7.3], 3-month 5.9 [4.1; 7.7], 12-month 8.2 [6.1; 10.4]; ASES-other symptoms difference: baseline 6.1 [4.6; 7.7], 3-month 6.4 [4.8; 8.0], 12-month 8.2 [6.3; 10.1]).</p><p><strong>Conclusions: </strong>Metabolic conditions were associated with lower PA and self-efficacy, with differences increasing with the number of co-existing conditions. The baseline disparities associated with metabolic conditions persisted after the intervention, with both groups showing improvement at 3 months but reverting to baseline by 12 months. This suggests that current guideline-based interventions for OA may not reduce long-term disparities related to metabolic conditions.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of global practices in the management of colchicine-resistant familial Mediterranean fever: a CliPS network analysis.","authors":"Fatih Haslak, Nimet Oner, Inès Elhani, Tanja Hinze, Anna Mamutova, Rim Bourguiba, Muserref Kasap Cuceoglu, Konstantinos Pateras, Yonatan Butbul Aviel, Marion Delplanque, Roberta Caorsi, Mario Šestan, Stéphanie Ducharme Bénard, Jürgen Brunner, Majdouline El Moussaoui, Meri Kirijas, Tamas Constantin, Sonia Carriquí Arenas, Ghalia Khellaf, Vafa Guliyeva, Naiera Assalia, Stefan Backes, Betul Sozeri, Michaël Hofer, Nuray Ayaz, Helen Lachmann, Helmut Wittkowski, Véronique Hentgen","doi":"10.1136/rmdopen-2025-006097","DOIUrl":"10.1136/rmdopen-2025-006097","url":null,"abstract":"<p><strong>Background: </strong>Although colchicine is the mainstay of familial Mediterranean fever (FMF) treatment, 5-10% of patients are considered to have colchicine resistance (CR). However, there is no globally agreed CR definition or indications for biological disease-modifying anti-rheumatic drugs (bDMARDs).</p><p><strong>Methods: </strong>A survey on 'Biologics in Monogenic Autoinflammatory Diseases', part of the 'Clinical Practice Strategies' (CLiPS) initiative, was conducted by a JIR cohort-initiated eCOST network among expert participants worldwide. Our primary aim was to provide a flowchart reflecting the different CR definitions and present data regarding bDMARD indications. The secondary aim was to determine how specific biases influence clinical approaches. We analysed the CliPS according to the experience levels of physicians, country-specific FMF prevalence, countries' gross domestic product, bDMARD availability and reimbursement policies of the countries.</p><p><strong>Results: </strong>A total of 223 responses from 46 countries were included in the study. Almost half of the respondents (73/160, 45.6%) indicated that three to four attacks within the preceding 6 months were necessary for their CR definition. The most frequently used acute-phase reactant was C-reactive protein (157/164, 95.7%). Almost three-fourths of the respondents (74%, n=165) considered that supplementary factors, including complications of FMF, attack severity, elevated activity scores, patient-reported outcome and quality of life scales, influenced their CR definition.</p><p><strong>Conclusion: </strong>We present a novel flowchart describing physicians' general attitudes and unique findings regarding management strategies for colchicine-resistant FMF and shifting trends influenced by epidemiological and socioeconomic factors.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data-driven identification of subgroups in early rheumatoid arthritis: mortality and cardiovascular disease in a cohort from western Norway.","authors":"Christian Lillebø Alsing, Jannicke Igland, Tone Wikene Nystad, Helga Midtbø, Eirik Ikdahl, Halvor Næss, Salman Zarar, Bjørg-Tilde Svanes Fevang","doi":"10.1136/rmdopen-2025-005905","DOIUrl":"10.1136/rmdopen-2025-005905","url":null,"abstract":"<p><strong>Aim: </strong>To identify subgroups of early rheumatoid arthritis (RA) based on comorbidities and RA manifestations and to investigate their associated risks of cardiovascular events and mortality.</p><p><strong>Methods: </strong>We included patients with incident RA, diagnosed during 2002-2013 and followed through 2022. Latent class analysis was performed using 29 variables (excluding age) to identify subgroups 1 year after RA diagnosis. Risk of major cardiovascular events (4p-MACE), death, acute coronary syndrome and stroke was compared between groups using Cox regression adjusting for age and sex.</p><p><strong>Results: </strong>Four subgroups were identified in a cohort of 873 patients with early RA: a 'cardiometabolic' group (19%), characterised by a high prevalence of cardiovascular disease (CVD) and diabetes; an 'elderly-onset' group (20%), with a high prevalence of polymyalgia rheumatica, anticitrullinated protein antibodies (ACPAs) negativity and less use of disease-modifying antirheumatic drugs (DMARDs); a 'classic' group (26%) with extensive joint involvement and the highest C reactive protein (CRP) levels and a 'young-onset' group (35%) characterised by ACPA positivity and palindromic arthritis.Compared to the 'young-onset' subgroup, both the 'cardiometabolic' (HR 2.14, 95% CI 1.20 to 3.79) and 'elderly-onset' subgroups (HR 1.89, 95% CI 1.07 to 3.35) had increased MACE risk. However, only the 'cardiometabolic' subgroup had increased mortality risk (HR 1.79, 95% CI 1.12 to 2.87).</p><p><strong>Conclusion: </strong>Four distinct subgroups were identified with different clinical profiles and outcomes. This underscores the feasibility of data-driven classification in early RA. The 'cardiometabolic' and 'elderly-onset' subgroups had similarly high MACE risk, but the latter used less DMARDs, antihypertensives and statins, suggesting undertreatment of both RA and CVD risk factors.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased GPR55 expression links B-cell activation and vascular remodelling in atherosclerosis in patients with early rheumatoid arthritis.","authors":"Daniel Miranda-Prieto, Mercedes Alperi-López, Ángel I Pérez-Álvarez, Sara Alonso-Castro, Ana Suárez, Javier Rodríguez-Carrio","doi":"10.1136/rmdopen-2025-005820","DOIUrl":"10.1136/rmdopen-2025-005820","url":null,"abstract":"<p><strong>Objective: </strong>Inflammation and repair responses may be involved in atherosclerosis in rheumatoid arthritis (RA), although mechanisms are unknown. GPR55, a cannabinoid receptor expressed in haematopoietic and stromal tissues, has been implicated in atherosclerosis in mouse models, but evidence in humans is lacking. Our aim was to evaluate GPR55 expression in leucocyte populations in RA and their potential role in atherosclerosis.</p><p><strong>Methods: </strong>GPR55 expression was quantified by flow cytometry in 63 treatment-naïve patients with RA, 11 individuals with arthralgia and 36 controls. Atherosclerosis was assessed by Doppler ultrasound. Cytokines were measured by immunoassays, and serum proteomics were performed by a high-throughput targeted panel. In vitro cultures were performed with mononuclear cells from healthy donors.</p><p><strong>Results: </strong>Decreased GPR55 expression in B-cells and monocytes was found in RA, whereas no differences were observed in arthralgia. Public datasets validated these findings. B-cell GPR55 expression was unrelated to clinical features, risk factors and atherosclerosis in RA, but exhibited divergent associations with leucocyte populations. GPR55 expression was associated with proinflammatory cytokines, immunoglobulin and antibody levels, metabolomic markers of inflammation and proteomic signatures related to vascular remodelling and B-cell responses in RA. These associations were dependent on the atherosclerosis status. Lipopolysaccharide exposure in vitro decreased GPR55 expression in B-cells in a dose-dependent manner, which overlapped increasing CB86 expression.</p><p><strong>Conclusions: </strong>Reduced GPR55 expression hallmarked B-cells and monocyte subsets in early RA. GPR55 expression was linked to B-cell activation-related pathways, presumably via T-cell independent mechanisms and vascular remodelling. GPR55 may be a novel hub between immune circuits and maladaptive responses in atherosclerosis.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Idiopathic inflammatory myopathies lack neutralising autoantibodies to type- I, II and III interferons.","authors":"Anish Behere, Hedvig Mildner, Irene Peralta Garcia, César Pérez Bucio, Ingrid Lundberg, Begum Horuluoglu, Nils Landegren","doi":"10.1136/rmdopen-2025-005836","DOIUrl":"10.1136/rmdopen-2025-005836","url":null,"abstract":"<p><strong>Objective: </strong>To determine whether autoantibodies against interferons are present and play a role in disease modulation in idiopathic inflammatory myopathies (IIMs).</p><p><strong>Methods: </strong>We screened for autoantibodies against a large number of interferons (IFNs) and other cytokines in a cross-sectional observational cohort of Swedish patients with anti-synthetase syndrome (n=51) and dermatomyositis (n=48), matched together with blood donors (n=100) from general population, using both planar and suspension-based multiplex assays. A single patient with autoimmune polyendocrine syndrome, type-1 (APS-1), known to harbour autoantibodies that neutralise type-I interferons, was included as a reference biological positive. The functional ability of autoantibodies to neutralise type-I interferons was tested in vitro, using an IFN-α/β responsive cell reporter assay.</p><p><strong>Result: </strong>The initial screening of plasma samples indicated a repertoire of autoantibodies in IIM patients against a number of common myositis-specific and myositis-associated antigens. On screening for autoantibodies against type-I, II or III interferons, we did not find any evidence of anti-IFN autoantibodies being present in any of the IIM patient subgroups or the blood donors from general population. Additionally, none of the tested plasma samples, except the APS-1, exhibited neutralisation of physiological concentration IFN-α2, further confirming a complete lack of functional autoantibodies against IFN-α subtypes in this cohort.</p><p><strong>Conclusions: </strong>We did not detect neutralising autoantibodies against IFN-α and autoantibodies against other types of IFNs in a Swedish cohort of IIM patients. These findings contrast with the presence of autoantibodies against type-I IFNs in other systemic autoimmune diseases, such as systemic lupus erythematosus, characterised by type-I IFN overactivation.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METHOFRACT, a methotrexate osteopathy multicentre cohort study.","authors":"François Robin, Roba Ghossan, Nadia Mehsen-Cetre, Louise Triquet, Guillaume Larid, Guillaume Coiffier, Marine Mina, Marie Eva Pickering, Claire Barthe, Julien Paccou, Julien Herman, Emmanuel Massy, Isabelle Roitg, Martine Branquet, Julien Lasnier Siron, Manon Guillouard, Camille Desmonet Trousset, Aurore Aubrun, Bertrand Godfrin, Jean-Philippe Hauzeur, Emmanuel Chatelus, Eugénie Koumakis, Jean-Louis Legrand, Thierry Schaeverbeke, Alexia Leloix, Maeva Masson, Julia Nicolau, Charles Ghiringhelli, Marijke Decrock, Cécile-Audrey Durel, Béatrice Bouvard, Bernard Cortet, Charlotte Casadepax-Soulet, Olivier Malaise, Rose-Marie Javier, Karine Briot, Pascal Guggenbuhl","doi":"10.1136/rmdopen-2025-005941","DOIUrl":"10.1136/rmdopen-2025-005941","url":null,"abstract":"<p><p>Methotrexate-induced osteopathy (MTX-IO) is a rare condition typically involving the lower limbs, especially tibia or foot fractures, among patients with well-controlled rheumatoid arthritis (RA) or psoriatic arthritis (PsA). This study aimed to identify the affected population, describe fracture characteristics and identify risk factors for poor clinical outcome. A multicentre retrospective study included patients with MTX-IO diagnosed by bone specialists or identified through French pharmacovigilance. The data collected included clinical presentation, imaging features, bone mineral density and biochemical markers. Between 2012 and 2024, 92 patients were included, predominantly postmenopausal women with seropositive RA. A history of major fractures was noted for 22% of the patients, and 56% presented osteoporosis at diagnosis. Fractures were most common in the tibial metaphysis (distal and proximal) (88%) and the foot bones (49%), with multiple fractures often present at diagnosis (76%), and frequently repeated fractures in the patients' recent histories (63%). Diagnosis was conducted using MRI of the painful sites (84%), but bone scintigraphy was also used (41 patients, 45%). Management involved methotrexate discontinuation in 79% of the cases. Fracture healing and pain relief were achieved in 77% of the cases, with a significant difference in outcomes between those who discontinued methotrexate (91%) versus those who continued (29%) (p<0.001). MTX-IO is a rare but significant condition, especially among postmenopausal women with RA or PsA. Early diagnoses via MRI or bone scintigraphy and the discontinuation of methotrexate are critical, as stopping the drug significantly improves outcomes and prevents further fractures.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients with systemic lupus erythematosus (SLE) have an increased bisphenol A methylation score linked to SLE risk genes and selected clinical subphenotypes.","authors":"Holme Vestin, Nina Oparina, Maija-Leena Eloranta, Martina Frodlund, Iva Gunnarsson, Christopher Sjöwall, Elisabet Svenungsson, Lars Rönnblom, Juliana Imgenberg-Kreuz, Dag Leonard","doi":"10.1136/rmdopen-2025-006021","DOIUrl":"10.1136/rmdopen-2025-006021","url":null,"abstract":"<p><strong>Objectives: </strong>Bisphenol A (BPA), a xenoestrogen that can alter DNA methylation status, has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study aimed to investigate whether methylation changes at BPA-sensitive 5'-C-phosphate-G-3' (CpG) sites are associated with SLE and clinical subphenotypes.</p><p><strong>Methods: </strong>A discovery cohort (n=747) and a replication cohort (n=388) including Swedish patients with SLE and healthy controls were investigated using the Illumina HM450k bead chip. BPA-sensitive CpG sites were selected if differentially methylated in ≥2 of 7 BPA exposure studies and supported by cell line data. A BPA_All score including 19 CpGs and a BPA_SLE score based on three CpG sites co-localised in the genome with SLE risk loci were calculated for each individual, analysed for associations with clinical data and then compared with publicly available transcriptomic data from BPA-treated cells.</p><p><strong>Results: </strong>Patients with SLE had significantly higher BPA_SLE score than controls in the discovery (OR 1.34, p=4.6×10^-13), replication (OR 1.28, p=1.1×10^-5) and meta-analysis (OR 1.32, p=3.3×10^-17). Higher BPA_All score was associated with SLE in the discovery cohort (OR 1.05, p=2.3×10^-3) but not in the replication cohort (OR 1.04, p=0.12) with a significant difference in the meta-analysis (OR 1.05, p=7.0×10^-4). Both scores were associated with prednisolone treatment (p<0.001), and the BPA_SLE score was associated with serositis and autoantibodies (p<0.05). Transcriptomic analysis of BPA-treated cells revealed enrichment in pathways such as interferon and mitogen-activated protein kinase signalling.</p><p><strong>Conclusions: </strong>Our findings reveal a novel association between BPA exposure and DNA methylation changes in SLE, with potential implications for the regulation of immune-related gene expression.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of LUPIN: a patient-centred self-administered tool to assess disease activity and patient-reported outcomes in systemic lupus erythematosus.","authors":"Marc Scherlinger, Jean-Francois Kleinmann, Antonin Folliasson, Marianne Riviere, Sabine Malivoir, Raphaelle Rybak, Jean Sibilia, Zahir Amoura","doi":"10.1136/rmdopen-2025-006106","DOIUrl":"10.1136/rmdopen-2025-006106","url":null,"abstract":"<p><strong>Objective: </strong>To develop and validate LUPIN, a self-administered, patient-centred questionnaire codesigned by patients and lupus specialists to assess disease activity and patient-reported outcomes in systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>LUPIN and the SF-36 questionnaires were distributed across 34 centres in both metropolitan France and overseas territories. Patients completed the questionnaire prior to their consultations. Physicians, blinded to patients' responses, assessed disease activity using SLE Disease Activity Index 2000 (SLEDAI-2K) and Physician Global Assessment (PhGA). Correlations and discordances between patient and physician assessments were analysed.</p><p><strong>Results: </strong>Among 444 participants (85% women, mean age 45 years), the most common manifestations included joint (86%) and skin (72%) involvement; 35% had a history of lupus nephritis. While correlations between LUPIN scores and SLEDAI/PhGA were statistically significant but modest (r<0.39), stronger associations were observed with SF-36 domains for fatigue (r=0.65), pain (r=0.65), and physical function (r=0.69). In patients with active SLE (SLEDAI≥4; n=153), the correlation between LUPIN and clinical SLEDAI improved (r=0.53, p<0.0001). Discordances were primarily driven by patient-reported fatigue and pain, unrelated to suspected mechanical or central pain syndromes.</p><p><strong>Conclusion: </strong>LUPIN effectively captures symptom domains that are often under-represented in conventional clinical indices and reflects the lived burden of disease in SLE. It offers a practical, scalable tool to support patient engagement, shared decision-making and individualised disease monitoring. A longitudinal digital study is underway to further assess its value in tracking disease fluctuations over time.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}