Rheumatology最新文献

{"title":"Circulatory microRNA signature distinguishing rheumatoid arthritis and psoriatic arthritis.","authors":"Órla Tynan, Megan M Hanlon, Achilleas Floudas, Siobhán Wade, Ursula Fearon, Douglas J Veale","doi":"10.1093/rheumatology/keag246","DOIUrl":"https://doi.org/10.1093/rheumatology/keag246","url":null,"abstract":"<p><strong>Objectives: </strong>Gene regulatory microRNA (miRNA) have emerged as promising biomarkers and therapeutic targets in autoimmunity pathology. This study examines circulatory miRNA as cellular biomarkers that can distinguish rheumatoid arthritis (RA) from psoriatic arthritis (PsA) to evaluate the potential implications for disease pathogenesis.</p><p><strong>Methods: </strong>RA (n = 48) and PsA (n = 50) patients and healthy controls (HC) (n = 20) were recruited and serums obtained. Multiplex analysis of serum miRNAs was performed using the FirePlex miRNA Immunology-V2 panel (FirePlex Bioworks Inc.). DNA intelligent analysis (DIANA)-mirPath and STRING software were used to predict pathways targeted by the dysregulated miRNAs.</p><p><strong>Results: </strong>7 miRNAs; miR-126-3p, miR-29b-3p, miR-22-3p, miR-223-3p, miR-320a, let-7e-5p, and let-7g-5p were significantly elevated in RA serum compared with PsA (all p< 0.05), in addition to HC (all p< 0.05), with high sensitivity and specificity as determined by receiver-operating characteristic curve analysis. PCA and biplot analysis demonstrated differential miRNA clustering between both disease states with a dominant skew towards 3 specific miRNA in RA vs PsA; miR-29b-3p, miR-22-3p, and miR-223-3p. DIANA analysis and STRING visualisation of this miRNA signature identified downstream target pathways including PI3K-Akt and FoxO signalling, all importantly associated with aspects of RA pathogenesis including angiogenesis, invasion, and cell death.</p><p><strong>Conclusion: </strong>This study identified three key miRNAs demonstrating differential expression levels between RA and PsA, which potentially govern downstream inflammatory pathways regulating distinct disease mechanisms. Therefore, circulating miRNAs may be valuable as non-invasive diagnostic biomarkers that can distinguish RA from PsA and may additionally assist in elucidating differential disease pathogenesis.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857079","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":"Higher hydroxychloroquine dose based on actual body weight is associated with lower SLE flare risks while maintaining tolerability.","authors":"Shotaro Yamamoto, Takeo Sato, Katsuya Nagatani, Yasuo Nagafuchi, Kojiro Sato","doi":"10.1093/rheumatology/keag242","DOIUrl":"https://doi.org/10.1093/rheumatology/keag242","url":null,"abstract":"<p><strong>Objectives: </strong>The effects of hydroxychloroquine (HCQ) dose based on actual body weight (ABW) on systemic lupus erythematosus (SLE) remain unclear. We investigated the effects of HCQ dose based on ABW of patients with SLE.</p><p><strong>Methods: </strong>Patients were classified into ≥5 mg/kg ABW (high dose [HD]) and <5 mg/kg ABW (low dose [LD]) groups. Patient backgrounds were adjusted using inverse probability of treatment weighting method. The discontinuation rate owing to adverse events of overall cohort (group 1) was evaluated. Subgroups with a disease duration ≥1 year (group 2) and without additional immunosuppressive agents and biologics after HCQ initiation (group 3) were compared with evaluate flare-rates, prednisolone dose, and serological data.</p><p><strong>Results: </strong>Among 182 patients in group 1, 60 (33%) comprised the HD group. Five-year discontinuation rates were 18.9% and 13.6% in the HD and LD groups, respectively (p= 0.314). Three-year flare-free rates in HD groups were higher than those in LD group: 75.0% (HD) vs 60.7% (LD) (p= 0.239) in group 2, and 79.2% (HD) vs 57.8% (LD) (p= 0.141) in group 3. In group 3, each 0.2 mg/kg increase in the HCQ dose reduced flares (hazard ratio, 0.91; 95% confidence interval: 0.84-0.99).</p><p><strong>Conclusion: </strong>No clear differences in efficacy and safety were observed between the HD and LD groups; however, a higher HCQ dose was associated with a reduced flare risk. Our findings suggest that a lower HCQ dose may be associated with a higher flare risk in patients with SLE, highlighting the importance of HCQ dose based on ABW.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857081","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":"Synovial biopsy and tissue sampling in the management of rheumatoid arthritis.","authors":"Dario Bruno, Barbara Tolusso, Elisa Gremese, Costantino Pitzalis","doi":"10.1093/rheumatology/keag241","DOIUrl":"https://doi.org/10.1093/rheumatology/keag241","url":null,"abstract":"<p><p>Synovial tissue (ST) biopsy has evolved from an experimental procedure into a clinically relevant tool that provides unparalleled access to the inflamed joint in rheumatoid arthritis (RA). Initially performed through blind needle and arthroscopic techniques, the adoption of minimally invasive ultrasound-guided biopsy has enabled safe, reproducible, and patient-acceptable tissue sampling across large and small joints. Histopathological evaluation, including the Krenn Synovitis Score and recognition of distinct pathotypes, has provided diagnostic and prognostic insights, while comparative analyses have highlighted shared inflammatory pathways with osteoarthritis and psoriatic arthritis. The integration of high-dimensional technologies such as bulk and single-cell transcriptomics, spatial profiling, and proteomics has uncovered novel stromal and immune cell subsets and linked tissue signatures to therapeutic outcomes. Landmark biopsy-driven trials (R4RA and STRAP) have demonstrated the feasibility of stratifying treatment on the basis of synovial biology, positioning synovial biopsy as a cornerstone in the long journey towards precision RA management.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857066","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":"Second delivery rates and recurrence of adverse pregnancy outcomes in women with systemic lupus erythematosus: a nationwide population-based cohort study.","authors":"Aleksandra Antovic, Ngoc V Nguyen, Iva Gunnarsson, Anna Sandström, Elizabeth V Arkema","doi":"10.1093/rheumatology/keag243","DOIUrl":"https://doi.org/10.1093/rheumatology/keag243","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the rate of a second delivery and the recurrence of adverse pregnancy outcomes (APOs) in women with SLE compared with the general obstetric population.</p><p><strong>Methods: </strong>This nationwide population-based cohort study used Swedish registers to identify women with SLE who had a first singleton liveborn delivery after SLE diagnosis. Up to ten non-SLE comparators were matched on birth year and residence. Second delivery rates were evaluated among women whose first delivery occurred during 2003-2020, with follow-up for second deliveries until the end of 2021. Recurrence of ≥ 1 APO, preeclampsia, and preterm delivery was assessed among women with two deliveries during 2003-2022. Cox proportional hazards models estimated hazard ratios (HRs) for second delivery, and modified Poisson models estimated risk ratios (RRs) for APO recurrence, adjusted for maternal age, education, BMI, smoking, APOs, and caesarean section.</p><p><strong>Results: </strong>Second delivery rates were analyzed in 543 women with SLE and 17 218 comparators. Over a median follow-up of 2.3 years, incidence rates of second delivery were 156 and 176 per 1,000 person-years in women with and without SLE, respectively (adjusted HR 0.89, 95% CI 0.80-0.99). The adjusted HR was 0.78 (0.63-0.96) among women with ≥1 APO in the first pregnancy. Women with SLE had a higher risk of recurrence of APOs, including preeclampsia (RR 1.38), preterm delivery (RR 2.31), and any APO (RR 1.54).</p><p><strong>Conclusion: </strong>Women with SLE have a lower rate of a second delivery and a higher recurrence risk of APOs, highlighting the need for individualized reproductive counseling and close monitoring.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842245","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":"Patient-reported outcomes and disease activity in giant cell arteritis: a longitudinal registry-based study.","authors":"Hans Kristian Skaug, Bjørg Tilde Fevang, Jörg Assmus, Andreas P Diamantopoulos, Geirmund Myklebust, Lene K Brekke","doi":"10.1093/rheumatology/keag233","DOIUrl":"https://doi.org/10.1093/rheumatology/keag233","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this registry-based cohort study was to evaluate longitudinal associations between disease activity measures and patient-reported outcomes (PROs) in GCA, and to assess whether specific PRO domains reflect clinically active disease.</p><p><strong>Methods: </strong>Among all GCA patients registered in NorVas up to 12 December 2024, we selected patients who: 1) fulfilled the ACR 1990 classification criteria for GCA, 2) had two PROs recorded at least once, and 3) were included in NorVas at the time of diagnosis. HRQoL was assessed by RAND-12, using the physical (PCS) and mental composite scores (MCS) as outcomes. Visual analogue scales were used to assess pain, fatigue, and global disease assessment. The association between the PROs and disease activity were evaluated using linear mixed effects models. We assessed the PROs over time and the difference in PROs between active and inactive disease.</p><p><strong>Results: </strong>We included 256 patients in the study with a median of 3 observations each, and a total of 1003 observations. All examined PROs showed a significant difference between active and inactive disease at baseline. Statistically and clinically significant differences were retained during follow-up for RAND-12-PCS (11.19 [5.67, 16.71]), pain (-12.64 [-18.58, -6.70]) and global assessment (-9.92 [-15.48, -4.35]).</p><p><strong>Conclusions: </strong>Our study demonstrates a consistent association between PROs and disease activity in GCA, most pronounced for the physical component of HRQoL, pain and global assessment. Patients with active disease showed statistically and clinically significant differences in PRO scores compared with those in remission, both at baseline and throughout follow‑up. While no single PRO domain can replace formal disease activity assessment, patterns across pain, fatigue and patient global measures may signal active disease and warrant clinical reassessment. Taken together, these findings indicate that selected combinations of PROs may serve as a useful adjunct in the monitoring of GCA.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842206","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":"Risk of interstitial lung disease following COVID-19 infection in patients with autoimmune diseases: a retrospective cohort study.","authors":"Ying-Li Lin, Meng-Che Wu, Yu-Hsun Wang, Gema Hernández Ibarburu, James Cheng-Chung Wei","doi":"10.1093/rheumatology/keag228","DOIUrl":"https://doi.org/10.1093/rheumatology/keag228","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to determine the risk of developing interstitial lung disease (ILD) as a major post-COVID outcome in individuals with autoimmune diseases.</p><p><strong>Methods: </strong>This retrospective cohort study utilized data from the TriNetX U.S. Collaborative Network. The case group comprised individuals with autoimmune rheumatic diseases who contracted COVID-19, whereas the control group included those who remained uninfected during the follow-up period. Patient baseline characteristics were balanced using propensity score matching (PSM). The primary outcome was newly diagnosed ILD. A Cox proportional hazards regression model was employed to calculate PSM-adjusted hazard ratios (HRs). Kaplan-Meier curves and log-rank tests were used to evaluate survival differences.</p><p><strong>Results: </strong>The study included 174 256 individuals (26 768 COVID-19 cases and 147 488 controls) from January 1, 2020, to December 31, 2022. After propensity score matching, two cohorts of 26 763 individuals were identified, both with balanced baseline characteristics. During the follow-up period, the COVID-19 group exhibited a significantly higher risk of ILD (HR: 1.23; 95% CI: 1.10-1.36). Subgroup analyses by age, sex, and autoimmune disease consistently revealed higher risks in the COVID-19 group than in the control group.</p><p><strong>Conclusions: </strong>COVID-19 infection was identified as a risk factor for the development of ILD in patients with autoimmune diseases, highlighting the importance of vigilant pulmonary surveillance in this population. Nevertheless, these findings should be interpreted with caution due to potential residual confounding, diagnostic misclassification, and the heterogeneity of autoimmune diseases, which may mask disease-specific risk variations and lead to potential misattribution of ILD risk across different autoimmune conditions.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842238","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":"P084 What does paediatric rheumatology care look like? National insights from the Getting It Right First Time programme","authors":"Robert D Sandler, William K Gray, Gavin Cleary, Luke Martin, Lesley J Kay, Peter C Lanyon, Flora McErlane","doi":"10.1093/rheumatology/keag121.120","DOIUrl":"https://doi.org/10.1093/rheumatology/keag121.120","url":null,"abstract":"Background/Aims In England, the 2025 paediatricrheumatology Getting It Right First Time (GIRFT) report identified that carewas delivered by more than the 16 commissioned paediatric rheumatology providers.Understanding paediatric rheumatology care pathways is an important first steptowards meaningful data-driven improvement, designed to support equitableaccess to care for children and young people living with rheumatic conditions. Methods We extracted data fromHospital Episode Statistics (HES) for England for all outpatient encounterscoded to rheumatology or paediatric rheumatology for people ≤17 years of ageacross two financial years (2023/24 and 2024/25). Data pertaining to age, referral source, coded diagnoses, appointment type, and clerical outcomes wereanalysed descriptively. Results A total of 173,984 encountersinvolving 41,143 unique patients were recorded. Most encounters (72.5%) werecoded to commissioned providers, with 27.5% taking place elsewhere. The medianage at appointment was 13 years (interquartile range [IQR] 9-15 years). Newreferrals comprised 24% of encounters, with fewer than half (46%) referred fromgeneral practice, as opposed to being referred by other hospital specialties.Approximately 70% of encounters were attended, 20% were subject to patient orhospital cancellation and around 5% coded as patients not being brought to theappointment. Approximately 89% of encounters were conducted face to face, with11% being virtual. Approximately 25% of patients were discharged at their firstappointment. Around 80% of encounters lacked diagnostic coding. Conclusion Understanding the existingprovision of paediatric rheumatology care is a key precursor to coherent andeffective improvement, including development of accessible and meaningful carepathways, designed to support timely access to the best possible care. HES datademonstrate that over half of new referrals are made by secondary careproviders; advice and guidance opportunities therefore need to be accessibleacross both primary and secondary care. Since almost one-third of paediatric rheumatologycare is delivered by non-commissioned providers, commissioned providers need towork with local colleagues to ensure equitable cross-regional access tospeciality paediatric rheumatology multidisciplinary care. Recognising the highproportion of adolescent patients, teams need support to deliver accessible anddevelopmentally appropriate care. The paucity of diagnostic coding datarendered descriptions of case mix unfeasible and forms the subject of futurework. Disclosure R.D. Sandler: None. W.K. Gray: None. G. Cleary: None. L. Martin: None. L.J. Kay: None. P.C. Lanyon: None. F. McErlane: None.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147755250","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":"E089 Thoughts of people living with rheumatoid arthritis on a weekly rheumatoid arthritis disease activity monitoring tool","authors":"Tim Pickles, Janice Davies, Ernest Choy","doi":"10.1093/rheumatology/keag121.312","DOIUrl":"https://doi.org/10.1093/rheumatology/keag121.312","url":null,"abstract":"Background/Aims Regular assessment of disease activity (DA) is important and people living with rheumatoid arthritis (plwRA) would benefit from monitoring their DA using patient-reported outcome measures (PROMs). Complementing clinical practice with remote DA monitoring between clinic appointments provides better information for plwRA and healthcare professionals to make better decisions on treatments. New evidence shows that a PROM containing five items could be used as the basis for this tool. Ahead of creating a weekly RA DA monitoring tool, the PLAN-HERACLES study was designed to gather plwRA’s thoughts on aspects of such a tool. Methods A survey containing 48 questions covering topics such as usefulness, likelihood of being used, feasibility of a weekly schedule and reminder format was designed. Participants were given a preface to the tool to base their answers on. Participants had to confirm their age as 18 or over and that they had received a diagnosis of RA. This survey was advertised by the National Rheumatoid Arthritis Society (NRAS), opened on 11th June 2024 and closed on 29th July 2024. The survey was available from https://nras.org.uk/2024/05/14/plan-heracles/ and posted across NRAS’s social media accounts on Facebook, Instagram and X. Results There were 1298 eligible and consented survey participants. From their responses, it was evident that the tool was deemed useful, acceptable, and likely to be used, that the proposed weekly schedule was feasible and that reminders would be required. The NRAS webpage had 159 views and social media posts had 4968 impressions. Conclusion Given these positive results, we plan to create this tool, though the first step is to finalise the PROM. Grant applications will be submitted to undertake this research before looking towards funding the complex intervention development research with barriers and facilitators work and participatory events. This will involve NRAS and tool developer COHESION Medical Ltd. Disclosure T. Pickles: None. J. Davies: None. E. Choy: Honoraria; E.C. has received honoraria/or served as member of speakers’ bureaus from Abbvie, Bio-Cancer, Biocon, Biogen, Eli Lilly, Fresenius Kai, Galapagos, Janssen, Pfizer, Sanofi, UCB and Viatris. Member of speakers’ bureau; E.C. has received honoraria/or served as member of speakers’ bureaus from Abbvie, Bio-Cancer, Biocon, Biogen, Eli Lilly, Fresenius Kai, Galapagos, Janssen, Pfizer, Sanofi, UCB and Viatris. Grants/research support; E.C. has received research grants from Bio-Cancer, Biogen, Pfizer and Sanofi. Other; EC receives a stipend as Editor-in-Chief of Rheumatology (Oxford).","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"51 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147755291","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":"OA05 Consensus on a core domain set for foot and ankle disorders in rheumatic and musculoskeletal diseases: an international OMERACT Delphi consensus study","authors":"Lara Chapman, Anthony Redmond, Toby O Smith, Caroline A Flurey, Pamela Richards, Catherine Hofstetter, Hylton B Menz, Marian Hannan, Eiman Soliman, John Arnold, Yvonne Golightly, Beverley Shea, Philip G Conaghan, Peter Tugwell, Shawna Grosskleg, Philip Helliwell, Heidi Siddle","doi":"10.1093/rheumatology/keag121.005","DOIUrl":"https://doi.org/10.1093/rheumatology/keag121.005","url":null,"abstract":"Background/Aims Foot and ankle disorders are common in rheumatic and musculoskeletal diseases (RMDs), but there is a lack of high-quality evidence assessing the effectiveness of treatments for these disorders. A significant contributing factor is the heterogeneity of domains used across clinical trials to assess treatment effectiveness, hindering the ability to pool data in meta-analyses. The OMERACT Foot and Ankle Working Group is standardising domains to be measured and reported in all clinical trials for foot and ankle disorders in RMDs. Methods This was a modified Delphi consensus study, involving four rounds of online surveys. The first survey round consisted of a list of domains and their definitions, generated from the findings from previous literature reviews and qualitative interviews with 56 patients from eight countries. Following established OMERACT methodology, participants rated the importance of each domain on a scale of 1-9. In the second and third survey rounds, participants reviewed their own scores from the previous round alongside group responses (patients vs. HCPs/researchers), then re-rated each domain. Domain names and definitions were iteratively refined following participant feedback. Domains rated as critically important by ≥ 70% of both groups at the end of the third survey were taken into a final round, where each was rated as ‘in’ or ‘out’ of a mandatory core domain set. Circumstance-dependent core domains and domains for future consideration were agreed by the research team. Results A total of 126 participants (49 patients) from 15 countries completed all four survey rounds. The RMDs represented included rheumatoid arthritis, spondyloarthropathies, foot/ankle osteoarthritis, systemic lupus erythematosus, scleroderma, gout, and localised MSK disorders (e.g. Achilles tendinopathy). Five domains (pain intensity, pain when weightbearing, physical function (activities and participation), joint movement and treatment satisfaction were rated “in” by ≥ 70% participants and proposed as core domains (mandatory for all trials), two (structural pathology, healthcare expenses) were proposed as circumstance-dependent domains, and four (gait, footwear, emotional wellbeing and sleep) were deemed important for future consideration (Table 1). Conclusion This proposed core domain set will now go through endorsement by OMERACT. Further work is needed to identify appropriate outcome measurement instruments for each core domain. Disclosure L. Chapman: None. A. Redmond: None. T.O. Smith: None. C.A. Flurey: None. P. Richards: None. C. Hofstetter: None. H.B. Menz: None. M. Hannan: None. E. Soliman: None. J. Arnold: None. Y. Golightly: None. B. Shea: None. P.G. Conaghan: Consultancies; AbbVie/Abbott, Alfasigma, Eli Lilly, Enlivex, FormatoinBio, Genascence, Grunenthal, Kolon TissueGene, Levicept, Moebius, Novartis, Orion, Pacira, Stryker, Takeda. Member of speakers’ bureau; Novartis, Moebius, Kolon TissueGene, Eli Lilly, AbbVie/Abbott. P. Tugw","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"4 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147755072","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":"P142 When artificial intelligence meets autoimmunity: benchmarking automated and expert-guided whole exome sequencing of lupus-causing genes","authors":"Anastasia-Vasiliki Madenidou, Ian N Bruce, Gillian I Rice","doi":"10.1093/rheumatology/keag121.176","DOIUrl":"https://doi.org/10.1093/rheumatology/keag121.176","url":null,"abstract":"Background/Aims Whole-exome sequencing (WES) is increasingly used to investigate patients with suspected monogenic forms of systemic lupus erythematosus and other systemic autoimmune rheumatic diseases (SARDs). With the increasing use of AI-assisted variant interpretation tools, there is a need to evaluate their real-world utility against expert-guided approaches. In a SARD cohort, we compared the performance of AI-assisted and expert-guided WES analysis strategies in identifying disease-relevant variants within lupus-causing genes. Methods We analysed WES data, generated with Illumina NovaSeq6000, from 120 patients with SARD disease and 20 healthy controls. Two analytic strategies were applied using the same platform, Emedgene: (1) an AI-based approach and (2) a semi-automated approach. The platform offers a fully automated phenotype-based variant analysis using AI, resulting in a list of prioritised variants for each case that are more likely to be causative, labelled as “most likely”. The “most likely” variants were extracted in a spreadsheet for further analysis (Table 1). For the expert-guided approach, the Emedgene platform was used for the initial part of the analysis, as it allows the application of a preset of filters followed by the extraction of data for additional analysis (Table 1). Results Before analysing data outside the platform, a total of 2,906 variants likely to be causative were identified with the Emedgene AI tool across all cases (mean 20.8 variants per case) compared to 8,391 variants (mean 59.93 variants per case) with the expert-guided method (Table 1). The majority of variants with both methods were loss-of-function variants of frameshift: 1,623 variants (77.4%) with the AI-guided variant analysis and 8,044 (95.9%) with the semi-automated approach. A comparable number of variants (78 vs 56) in lupus-causing genes were identified at the end of the analysis with both methods (Table 1). Notably, a known pathogenic variant in PEPD (c.819-1G&amp;gt;A, homozygous), previously identified in a patient with monogenic SARD, was detected using both approaches. Conclusion AI-assisted WES analysis offers efficiency and standardisation, yet expert review remains essential to ensure clinically meaningful interpretation in autoimmune genomics. Further studies in well-characterised monogenic cohorts will delineate the optimal integration of AI into autoimmune genomics. Disclosure A. Madenidou: Honoraria; Boehringer Ingelheim. Grants/research support; Janssen. I.N. Bruce: Consultancies; AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono and UCB. Honoraria; speaker for AstraZeneca, GlaxoSmithKline and UCB. Grants/research support; Genzyme/Sanofi, GlaxoSmithKline, Roche, Jansen and UCB. G.I. Rice: Grants/research support; Janssen.","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147755149","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}