Seminars in arthritis and rheumatism最新文献

{"title":"Self-directed versus supervised exercise therapy program combined with digitally supported patient education for knee osteoarthritis: a randomised, parallel-group feasibility trial","authors":"Larissa Rodrigues Souto ,&nbsp;Marcella Ferraz Pazzinatto ,&nbsp;Danilo De Oliveira Silva ,&nbsp;Allison M. Ezzat ,&nbsp;Christian J. Barton","doi":"10.1016/j.semarthrit.2025.152787","DOIUrl":"10.1016/j.semarthrit.2025.152787","url":null,"abstract":"<div><h3>Introduction</h3><div>Research comparing self-directed and supervised exercise therapy for knee osteoarthritis (KOA) is limited. This study evaluates the feasibility of a randomised controlled trial (RCT) comparing self-directed and supervised exercise therapy combined with education for people with KOA.</div></div><div><h3>Materials and methods</h3><div>Participants with a clinical diagnosis of KOA, living in Greater Melbourne, were recruited via advertisements on community notice boards and on social media. Each attended two online education sessions and accessed the web-based ‘My Knee’ education and self-management toolkit to support their learning and exercise completion. Participants were then randomised to self-directed or supervised exercise therapy and encouraged to complete ≥12 exercise therapy sessions (2x week) over at least six weeks. Feasibility outcomes included recruitment, retention, data completion (monitored by checking the completion status of the questionnaires), education and exercise therapy sessions completion. Between group differences for Knee Injury and Osteoarthritis Outcome Score-12 (KOOS-12) and European Quality of Life 5 Dimensions 5-Level Version (EQ-5D-5L) estimated whether treatment effects were clinically meaningful (i.e. minimal detectable change contained within the 95 % confidence interval).</div></div><div><h3>Results</h3><div>Over 6-months, 67 people expressed interest, 26 were eligible, and 24 consented to participate. All participants attended both education sessions, and none dropped out. Eighty-eight percent (15/17) of self-directed and 57 % (4/7) of the supervised participants completed the logbook. Completed logbook data indicated ≥12 exercises sessions were completed by 93 % of self-directed and all supervised participants. All feasibility criteria were met, or can be addressed in future trials. Clinically meaningful treatment effects were contained within the 95 % CI for all KOOS-12 subscales and the EQ-5D-5L in the self-directed group.</div></div><div><h3>Conclusion</h3><div>A larger-scale non-inferiority RCT is feasible, with strategies to increase recruitment rate and data completion.</div></div><div><h3>Trial registration</h3><div>ANZCTR Registration (ACTRN12623000123640).</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152787"},"PeriodicalIF":4.6,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713023","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":"Effects of cumulative lifetime estrogen exposure on the clinical characteristics and courses in postmenopausal women with rheumatoid arthritis","authors":"Eun Hye Park ,&nbsp;Sang Tae Choi ,&nbsp;Jung Soo Song ,&nbsp;Eun Ha Kang ,&nbsp;Yun Jong Lee ,&nbsp;You-Jung Ha","doi":"10.1016/j.semarthrit.2025.152790","DOIUrl":"10.1016/j.semarthrit.2025.152790","url":null,"abstract":"<div><h3>Objectives</h3><div>To assess the effect of cumulative lifetime estrogen exposure (CLEE) on the course of rheumatoid arthritis (RA).</div></div><div><h3>Methods</h3><div>A total of 2878 postmenopausal women with RA from the Korean Observational Study Network for Arthritis Cohort were investigated at baseline and followed for 5 years. CLEEs were calculated by combining the reproductive span and duration of postmenopausal hormone replacement therapy. Patients with RA were classified into higher and lower CLEE groups using a median of 34 years.</div></div><div><h3>Results</h3><div>Patients with RA and a lower CLEE (<em>n</em> = 1602) showed significantly higher disease activity and more radiographic erosion than those with a higher CLEE (<em>n</em> = 1179) at baseline. The lower CLEE group demonstrated worse patient-reported outcomes (PROs) for pain, fatigue, sleep disturbance, functional disability, health-related quality of life, and global assessment of RA than the higher CLEE group at baseline (all <em>P</em> &lt; 0.01). The lower CLEE group showed increased Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire-Disability Index scores and decreased EQ-5D-utility values over 5 years after adjusting for confounders. Among patients with RA and an SDAI&gt;11 at baseline, the lower CLEE group was significantly less likely to achieve remission after adjusting for confounders (HR, 0.597 [95% CI 0.421–0.848], <em>p</em> = 0.004).</div></div><div><h3>Conclusions</h3><div>Patients with RA and lower CLEE had higher disease activity, more erosive disease, and worse PROs than those with a higher CLEE. Lower CLEE adversely affects longitudinal changes in disease activity and PROs and is associated with a lower likelihood of achieving clinical remission in RA.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152790"},"PeriodicalIF":4.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687437","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":"The use of ASDAS to evaluate disease activity and response to treatment in patients with axial spondyloarthritis starting the first biological drug: Are ASAS recommendations being followed?","authors":"Mariana Emília Santos ,&nbsp;Sofia Ramiro ,&nbsp;Désirée van der Heijde ,&nbsp;Robert Landewé ,&nbsp;Ana Rita Cruz-Machado ,&nbsp;Carla Campinho Ferreira ,&nbsp;Carlos Marques-Gomes ,&nbsp;Catarina Dantas Soares ,&nbsp;Cláudia Miguel ,&nbsp;Fernando Albuquerque ,&nbsp;Frederico Martins ,&nbsp;Lígia Silva ,&nbsp;Helena Santos ,&nbsp;Inês Almeida ,&nbsp;Miguel Bernardes ,&nbsp;Nikita Khmelinskii ,&nbsp;Paula Valente ,&nbsp;Pedro Miguel Teixeira ,&nbsp;Susana Emídio Matias ,&nbsp;Vanessa Fraga ,&nbsp;Alexandre Sepriano","doi":"10.1016/j.semarthrit.2025.152781","DOIUrl":"10.1016/j.semarthrit.2025.152781","url":null,"abstract":"<div><h3>Objectives</h3><div>To determine the proportion of patients with axial spondyloarthritis (axSpA) who had ASDAS calculated at baseline and at least once within two follow-up visits after starting their first bDMARD; and to evaluate the likelihood of meeting ASAS criteria for treatment continuation at 3 and 6 months.</div></div><div><h3>Methods</h3><div>Patients with axSpA from the <em>Reuma.pt</em> registry who initiated their first bDMARD and attended baseline, 3-month (3 M), and 6-month (6 M) visits were included. Availability of ASDAS at baseline was cross-tabulated with its availability in ≥1 follow-up visit. When ASDAS was absent, the use of alternative outcome measures was evaluated. Treatment response (∆ASDAS ≥1.1) at 3 M and 6 M was analyzed across four response patterns: no response, 3 M only, 6 M only, or both.</div></div><div><h3>Results</h3><div>A total of 666 patients were included. Most had ASDAS at baseline (<em>N</em> = 540; 81 %), and 493 (74 %) also had ASDAS at 3 M and/or 6 M. No alternative outcome measure was predominantly used when ASDAS was absent. Among 336 patients with complete ASDAS evaluation, 58 % met ASAS continuation criteria at 3 M and 60 % at 6 M, with 86 % of response maintenance between 3 M and 6 M. Additionally, 25 % of 147 non-responders at 3 M responded at 6 M. Responders at both timepoints were more often male (65 % vs 45 %) and younger (mean age 35 vs 38 years).</div></div><div><h3>Conclusion</h3><div>ASDAS is widely assessed in axSpA patients starting bDMARDs by Portuguese rheumatologists. Most patients respond within 3 months but waiting until 6 months to determine treatment continuation is reasonable.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152781"},"PeriodicalIF":4.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703861","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":"Soft water exposure increases the effect of genetic susceptibility on the risk of rheumatoid arthritis","authors":"Dandan Tian ,&nbsp;Panlong Li ,&nbsp;Lijuan Chen ,&nbsp;Chun Huang ,&nbsp;Shan Tian ,&nbsp;Yuna Li ,&nbsp;Junting Yang ,&nbsp;Yuan Qiao ,&nbsp;Shanshan Cao ,&nbsp;Chaohua Cong ,&nbsp;Lei Zhao ,&nbsp;Jingjing Su ,&nbsp;Ying Wang ,&nbsp;Min Liu ,&nbsp;Yibin Hao","doi":"10.1016/j.semarthrit.2025.152788","DOIUrl":"10.1016/j.semarthrit.2025.152788","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is influenced by both genetic and environmental factors. The mineral content of domestic water plays an essential role in human health. However, the relationship between water mineral content, genetic predisposition, and RA risk remains unclear.</div></div><div><h3>Methods</h3><div>This observational study included 434,958 individuals to investigate the association between mineral content in domestic water, genetic risk, and the incidence of RA. The cohort comprised RA-free participants with complete data on water mineral levels, genetic profiles, lifestyle factors, and physical measurements at baseline. A polygenic risk score (PRS) for RA was calculated for each participant to assess genetic susceptibility. Cox regression models were used to examine associations between water mineral concentrations, PRS, and RA risk. Stratified analyses were performed to evaluate the modifying effect of water mineral content on genetic risk.</div></div><div><h3>Results</h3><div>During a median follow-up of 15 years, 5880 new RA cases were recorded. After adjusting for multiple covariates, higher concentrations of calcium carbonate in domestic water were associated with a reduced risk of RA (hazard ratio [HR] = 0.93; 95 % confidence interval [CI]: 0.90 to 0.95; <em>p</em> = 1.74 × 10⁻⁹). Individuals in the highest PRS tertile had a 53 % to 74 % increased risk of RA compared to those in the lowest tertile. Notably, those with both the highest PRS and exposure to soft water had a 92 % (95 % CI: 71 % to 115 %) increased risk of RA compared to individuals with the lowest PRS and exposure to very hard water. Multiple sensitivity analyses confirmed the robustness of these findings.</div></div><div><h3>Conclusions</h3><div>These results suggest that exposure to hard water may reduce the risk of RA, particularly in individuals with high genetic susceptibility.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152788"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679174","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":"Efficacy and safety of anti-Tumor Necrosis Factor-α biosimilars in Juvenile Idiopathic Arthritis - a systematic review and meta-analysis","authors":"Junjie Huang ,&nbsp;Kai Liang Teh ,&nbsp;Chunliang Chen ,&nbsp;Lena Das ,&nbsp;Thaschawee Arkachaisri","doi":"10.1016/j.semarthrit.2025.152792","DOIUrl":"10.1016/j.semarthrit.2025.152792","url":null,"abstract":"<div><h3>Objectives</h3><div>Anti-Tumor Necrosis Factor-α (aTNF) biologics have transformed the management of Juvenile Idiopathic Arthritis (JIA), but their high-cost limits access. Biosimilars provide an affordable alternative. We aimed to summarize the data on the efficacy and safety profiles of aTNF biosimilars in JIA.</div></div><div><h3>Methods</h3><div>A systematic search was conducted through the Cochrane Library, Embase, PubMed, Scopus, and Web of Science. Studies evaluating the use of aTNF biosimilars in JIA patients compared against originators or placebo, published from inception to 30th August 2024, were included. Quality of included studies was assessed by the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. Efficacy and safety outcomes were summarized descriptively, and meta-analysis was performed where appropriate. (PROSPERO Registration ID: CRD42024523627)</div></div><div><h3>Results</h3><div>Five observational studies were identified. Risk of bias was assessed to be serious in all studies. All but one study showed no significant difference between biosimilars and originators in head-to-head comparisons of disease activity measured using Juvenile Arthritis Disease Activity Scores (JADAS). In two studies on switching of originators to biosimilars, disease activities remained stable after switch until the end of study follow-up. Adverse events were similar between biosimilars and originators (OR 0.78, 95%CI: 0.52-1.17).</div></div><div><h3>Conclusion</h3><div>Biosimilars and originators of aTNF are similar in efficacy and safety in pediatric patients with JIA. However, there is a lack of high-quality studies. This review should be updated as more studies become available.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152792"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703860","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":"Estimating the incidence of autoimmune inflammatory arthritis after Lyme disease","authors":"John B Miller ,&nbsp;Brittany L Adler ,&nbsp;Ana-Maria Orbai ,&nbsp;Ami A Shah ,&nbsp;Elizabeth Szymanski ,&nbsp;Laura M Prichett ,&nbsp;John N Aucott","doi":"10.1016/j.semarthrit.2025.152797","DOIUrl":"10.1016/j.semarthrit.2025.152797","url":null,"abstract":"<div><h3>Objective</h3><div>A previous case series described the development of new autoimmune, inflammatory arthritis (IA) developing within 2 years of Lyme disease (LD). This study aimed to estimate the incidence of IA following LD using administrative claims data. Influenza, an infection not typically associated with post-infectious IA, was used for comparison.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study using the Johns Hopkins Health System administrative claims data from 01/2013–05/2024. Patients with LD and influenza were identified using International Classification of Diseases (ICD) codes, with LD cases further defined by requiring an antibiotic prescription within 30 days of the ICD code. IA cases were identified using 2+ ICD codes for rheumatoid arthritis, psoriatic arthritis or spondyloarthritis. Comparisons between infection groups were conducted using chi-square tests and Z-tests as appropriate. Logistic regression analyses were conducted to estimate the odds of IA development within two years of Lyme or influenza diagnosis, controlling for age and sex.</div></div><div><h3>Results</h3><div>The incidence of IA was significantly higher following LD compared to influenza (1.67 % vs 0.45 %, <em>p</em> &lt; 0.0001), with the highest incidence of IA occurring within the first year after LD. Regression analysis showed LD was associated with increased odds of IA compared to influenza (OR 3.76, 95 % CI: 2.41–5.86, <em>p</em> &lt; 0.001) after adjusting for age and sex.</div></div><div><h3>Conclusion</h3><div>The incidence of IA was higher within a year of LD infection, higher than that expected in the general population. The temporal association and elevated incidence support the need for prospective studies to elucidate mechanisms linking infection and autoimmunity in LD.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152797"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687438","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":"Weight loss, disease activity, and patient reported outcomes in patients with musculoskeletal and autoimmune diseases taking weight loss medications: a retrospective cohort study","authors":"Thomas R. Riley ,&nbsp;Kristin Wipfler ,&nbsp;Katherine D. Wysham ,&nbsp;Veena K. Ranganath ,&nbsp;Michael D. George ,&nbsp;Kaleb Michaud ,&nbsp;Joshua F. Baker","doi":"10.1016/j.semarthrit.2025.152783","DOIUrl":"10.1016/j.semarthrit.2025.152783","url":null,"abstract":"<div><h3>Introduction</h3><div>Given potential impacts of adiposity on pain and inflammation, we evaluated if weight loss was associated with improvements in disease activity and patient reported outcomes (PROs) in people with rheumatic and musculoskeletal disease (RMD) using weight loss therapies.</div></div><div><h3>Methods</h3><div>Participants with RMDs enrolled in the <em>FORWARD</em> Databank and reporting weight loss medication use were included in this retrospective cohort study. Linear models using generalized estimating equations assessed the association with ≥5 % weight loss and changes in PROs and disease activity over a 6-month period, clustering by participant and adjusting for the prior 6-month PRO, BMI, diabetes status, age, and sex. Testing for effect modification was performed to assess whether the effect of weight loss varied across BMI categories and across condition.</div></div><div><h3>Results</h3><div>We identified 3868 users of weight loss medications with 24,484 discrete observations. Weight loss ≥5 % was reported in 10.5 % (2603) of observations and was associated with improvements in patient activity scale II (PAS-II), patient global assessment, pain, fatigue, polysymptomatic distress, and SF-36 physical component score (PAS-II adjusted: B -0.12, 95 % CI -0.17, -0.067, p &lt; 0.001). Those who lost ≥5 % of weight were more likely to have improvements in PAS-II and PROs if they were obese, independent of diagnosis.</div></div><div><h3>Conclusion</h3><div>Among participants with RMDs that reported weight loss medication use, ≥5 % weight loss was associated with statistically significant improvements in patient-reported disease activity and quality of life PROs. The use of weight loss medications could be considered in trials aimed at improving symptoms of RMDs.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152783"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703863","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":"Response to: ‘Critical Commentary ‘Infectious complications of Belimumab with standard care in systemic lupus erythematosus: A systematic review and meta-analysis’ by Saketh Sainag Mandiga et al","authors":"Yu Zhao ,&nbsp;Huihe Chen ,&nbsp;Weijie Wang","doi":"10.1016/j.semarthrit.2025.152784","DOIUrl":"10.1016/j.semarthrit.2025.152784","url":null,"abstract":"","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152784"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670676","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":"Developing efficient predictive models for the diagnosis of VEXAS syndrome","authors":"Daniel Montes ,&nbsp;Andrew C. Hanson ,&nbsp;Hannah E. Langenfeld ,&nbsp;Cynthia S. Crowson ,&nbsp;Mrinal M. Patnaik ,&nbsp;Ronald S. Go ,&nbsp;Alexander Hines ,&nbsp;Kambiz Kalantari ,&nbsp;Yael Kusne ,&nbsp;Terra Lasho ,&nbsp;Abhishek Mangaonkar ,&nbsp;Horatiu Olteanu ,&nbsp;Kaaren K. Reichard ,&nbsp;Megan M. Sullivan ,&nbsp;David S. Viswanatha ,&nbsp;Kenneth J. Warrington ,&nbsp;Matthew J. Koster","doi":"10.1016/j.semarthrit.2025.152796","DOIUrl":"10.1016/j.semarthrit.2025.152796","url":null,"abstract":"<div><h3>Objectives</h3><div>To identify clinical and laboratory features associated with the presence of <em>UBA1</em> mutation and develop predictive models to guide efficient diagnosis of VEXAS syndrome.</div></div><div><h3>Methods</h3><div>All patients who underwent <em>UBA1</em> mutation testing were identified. Using a comprehensive list of VEXAS syndrome features, the presence or absence of each feature in each patient was determined for two timepoints: time of first VEXAS symptom onset and the time of <em>UBA1</em> mutation testing. For each timepoint, the presence of each disease feature was compared between <em>UBA1</em> positive and negative patients. The least absolute shrinkage and selection operator (LASSO) method was used to develop multi-feature models to predict the presence of pathogenic <em>UBA1</em> mutations.</div></div><div><h3>Results</h3><div>Overall, 144 patients who underwent <em>UBA1</em> mutation testing were included. Features including skin rash, chondritis, and monocytopenia were significantly associated with the presence of a <em>UBA1</em> mutation at both timepoints. Macrocytosis, uveitis, and pulmonary disease had significant association at time of testing. 12-feature and 5-feature LASSO models at symptom onset demonstrated good discriminatory capacity with areas under receiver operating curves (AUCs) of 0.86 and 0.81, respectively. 16-variable and 5-feature models at time of testing had good-to-excellent performance with AUCs of 0.92 and 0.84, respectively. A single feature model utilizing absolute monocyte count also had fair discriminatory capacity with AUC of 0.78 at both timepoints.</div></div><div><h3>Conclusions</h3><div>Multi-feature models that efficiently separate VEXAS cases from controls were successfully developed. These models have the potential to address existing diagnostic challenges including a lack of consensus regarding key features of VEXAS syndrome.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152796"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703862","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":"Genome-wide association study for loci associated with positive antinuclear antibodies","authors":"Jing Cui ,&nbsp;Jeong Yee ,&nbsp;Hongshu Guan ,&nbsp;Jack Ellrodt ,&nbsp;Emily G. Oakes ,&nbsp;Liming Liang ,&nbsp;Karen H. Costenbader","doi":"10.1016/j.semarthrit.2025.152794","DOIUrl":"10.1016/j.semarthrit.2025.152794","url":null,"abstract":"<div><h3>Background</h3><div>The genetic basis, heritability, and genetic differences by patterns and titers of antinuclear antibodies (ANA) are still poorly understood.</div></div><div><h3>Methods</h3><div>Within the Mass General Brigham Biobank, containing electronic health records (EHR) and genotyping for &gt;65,000 consented patients, we identified individuals with HEp-2 immunofluorescence ANA results (1989–2022) and genetically predicted European ancestry. We performed genome-wide associated studies for ANA+ ≥ 1:40, ≥ 1:80, all and in speckled and homogeneous ANA patterns, for those only +1:40, and then excluding those with ≥1 of 9 ANA-associated autoimmune diagnoses, each compared to those ANA- and adjusted for age, sex, and 4 genetic principal components. The lability method estimated ANA+ heritability. We investigated HLA alleles using SNP2HLA imputation.</div></div><div><h3>Results</h3><div>7035 subjects were ANA+ at ≥1:40, 4279 at ≥1:80 and 5840 were ANA -. Associations were similar but stronger for ANA ≥1:80 than ≥1:40. Associations were stronger for speckled and homogeneous ANA patterns separately (each vs. all ANA-) and attenuated after excluding those with ≥1 autoimmune disease diagnosis. At both titers, <em>HLA-DQB1:0201</em> had the strongest association, OR 1.3 (95 % CI 1.2–1.5, p 9.1 × 10^–14 for ANA ≥1:80); <em>HLA-B:08, HLA-DRB1:03,</em> and <em>HLA:C:0701</em> alleles also showed significant associations. The strongest non-HLA association was rs34748780 (chromosome 7) near <em>IRF5/TNPO3,</em> OR 1.2 (95 % CI 1.1–1.4, p 1.6 × 10^–8 for ANA ≥1:80). ANA+ ≥1:40 heritability was 12 % (SE 0.03), p 1.0 × 10^–8 and ≥1:80 was 19 % (SE 0.03), p 1.9 × 10^–12.</div></div><div><h3>Conclusion</h3><div><em>HLA-DQB1:0201, HLA-DRB1:03, HLA-B,</em> and <em>HLA-C</em> were strong genetic factors for ANA+ in these European ancestry individuals.</div></div>","PeriodicalId":21715,"journal":{"name":"Seminars in arthritis and rheumatism","volume":"74 ","pages":"Article 152794"},"PeriodicalIF":4.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687439","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}