Annals of the Rheumatic Diseases最新文献

{"title":"Development of CARRA/PReS-endorsed consensus Core and Expanded Datasets in childhood-onset systemic lupus erythematosus for international registry-based research.","authors":"Rebecca E Sadun, Jennifer C Cooper, Alexandre Belot, Tadej Avcin, Amita Aggarwal, Jenny Ainsworth, Alisha Akinsete, Stacy P Ardoin, Michael W Beresford, Lynette Bortey, Hermine I Brunner, Joyce C Chang, Coziana Ciurtin, Ashley Daftary, Barbara Eberhard, Candace H Feldman, Christian M Hedrich, Aimee O Hersh, Linda T Hiraki, David A Isenberg, Sylvia Kamphuis, Andrea M Knight, Lou Lambert, Deborah M Levy, Stephen D Marks, Naomi Maxwell, Angela Migowa, Katharine Moore, Seza Ozen, Rosalind Ramsey-Goldman, Angelo Ravelli, Bryce B Reeve, Tamar B Rubinstein, Claudia Saad-Magalhaes, Sujata Sawhney, Laura E Schanberg, Emily von Scheven, Christiaan Scott, Mary Beth Son, Gladys Tony, Elissa R Weitzman, Scott E Wenderfer, Alisha Woodside, Laura B Lewandowski, Eve Md Smith","doi":"10.1136/ard-2024-226528","DOIUrl":"10.1136/ard-2024-226528","url":null,"abstract":"<p><strong>Objectives: </strong>Childhood-onset systemic lupus erythematosus (cSLE), representing 15%-20% of individuals with SLE, has been difficult to study globally due to differences between registries. This initiative, supported by Childhood Arthritis Rheumatology Research Alliance (CARRA) and Paediatric Rheumatology European Society (PReS), aims to create Core and Expanded cSLE Datasets to standardise and enhance research worldwide.</p><p><strong>Methods: </strong>21 international cSLE experts and 4 patients participated in a Delphi process (questionnaires, 2 topic-specific focus groups and 3 virtual consensus meetings) to create 2 standardised cSLE datasets. The Core cSLE Dataset was designed to include data essential to meaningful clinical research across many settings. The Expanded cSLE Dataset was designed for centres able to consistently collect data to address broader research questions. Final data items for the Core and Expanded datasets were determined by consensus defined as >80% agreement) using an adapted nominal group technique and voting.</p><p><strong>Results: </strong>The resulting Core cSLE Dataset contains 46 items, including demographics, clinical features, laboratory results, medications and significant adverse events. The Expanded cSLE Dataset adds 26 additional items and includes patient-reported outcomes. Consensus was also achieved regarding the frequency and time points for data collection: baseline, quarterly follow-up visits, annually and flare visits.</p><p><strong>Conclusion: </strong>Standardised Core and Expanded cSLE Datasets for registry-based international cSLE research were defined through the consensus of global experts and patient/caregiver representatives, endorsed by CARRA and PReS. These datasets incorporate disease-specific and patient-specific features, optimised for diverse settings to facilitate international collaborative research for children and adolescents with SLE worldwide.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"158-168"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370164","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":"Real-life use of the PEXIVAS reduced-dose glucocorticoid regimen in granulomatosis with polyangiitis and microscopic polyangiitis.","authors":"Sophie Nagle, Yann Nguyen, Mary-Jane Guerry, Thomas Quemeneur, Dimitri Titeca-Beauport, Thomas Crépin, Rafik Mesbah, Idris Boudhabhay, Grégory Pugnet, Céline Lebas, Antoine Néel, Alexandre Karras, Eric Hachulla, Juliette Woessner, Vincent Pestre, Raphaël Borie, Stephane Vinzio, Jean-Baptiste Gouin, Sara Melboucy-Belkhir, Roderau Outh, Benjamin Subran, Mathieu Gerfaud-Valentin, Sebastien Humbert, Philippe Kerschen, Yurdagul Uzunhan, Tiphaine Goulenok, Maxime Beydon, Nathalie Costedoat-Chalumeau, Xavier Puechal, Benjamin Terrier","doi":"10.1136/ard-2024-226339","DOIUrl":"10.1136/ard-2024-226339","url":null,"abstract":"<p><strong>Background: </strong>The PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC.</p><p><strong>Methods: </strong>We conducted a retrospective, multicentre study comparing PEXIVAS redGC with standGC in patients with AAV. The primary composite outcome was the occurrence of death, ESKD, AAV progression before remission or relapse within the 12 months following induction. Inverse probability of treatment weighting was used to correct for baseline imbalance between groups. Factors associated with the occurrence of the primary outcome were estimated.</p><p><strong>Results: </strong>A total of 234 patients were included. The primary composite outcome occurred in 42/126 (33%) patients with redGC versus 20/108 (19%) with standGC. In unweighted multivariable analysis and in weighted analysis, redGC was independently associated with the primary outcome but not with death or ESKD. Among redGC-treated patients, those with serum creatinine>300 µmol/L were more likely to achieve the primary outcome. RTX-treated patients who received redGC were more likely to experience death or ESKD and to achieve the primary outcome.</p><p><strong>Conclusion: </strong>In this study of patients with AAV primarily treated with RTX, redGC was associated with an increased risk of the primary outcome consisting of death, ESKD, AAV progression before remission or relapse.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"319-328"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370212","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":"Evaluation and prediction of relapse risk in stable systemic lupus erythematosus patients after glucocorticoid withdrawal (PRESS): an open-label, multicentre, non-inferiority, randomised controlled study in China.","authors":"Yunyun Fei, Lidan Zhao, Lijun Wu, Xiaoxia Zuo, Rongli Li, Jiaomei Cheng, Hui Luo, Xue Wu, Li Sun, Jingjing Xu, Yingxuan Zhu, Yang Wang, Zhu Chen, Xiaomei Li, Xiaofei Wang, Xuan Zhang","doi":"10.1136/ard-2024-225826","DOIUrl":"10.1136/ard-2024-225826","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the relapse rate after glucocorticoid (GC) withdrawal with or without hydroxychloroquine (HCQ) maintenance in sustained clinically inactive systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>The PRESS trial is a multicentre, 33-week, open-label, three-arm, non-inferiority designed, randomised controlled trial. SLE patients with sustained clinically inactive disease who maintained on low-dose GC plus HCQ therapy were screened and qualified patients were randomly assigned to three groups: drug-free group (both GC and HCQ withdrew); HCQ group (discontinued GC but maintained HCQ); dual maintenance group (both GC and HCQ continued). The primary endpoint was to compare the proportion of patients experiencing a relapse as defined by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index flare index by 33 weeks. Two parallel non-inferiority analyses were performed (drug-free group vs dual maintenance group and HCQ group vs dual maintenance group).</p><p><strong>Results: </strong>From 3 November 2016 to 13 August 2021, 333 participants complied with the protocol after randomisation were analysed. The relapse rates in the three groups were 26.1%, 11.2% and 4.7%, respectively. Compared with dual maintenance group, drug-free group failed to achieve non-inferiority significance (relapse rate difference 21.4%; 95% CI 12.3% to 30.5%; Pnon-inferiority=0.238), whereas HCQ group achieved non-inferiority (relapse rate difference 6.5%; 95% CI -0.5% to 13.5%; Pnon-inferiority=0.034). HCQ group also exhibited fewer relapses than drug-free group (p=0.006). Adverse events were similar among all three groups.</p><p><strong>Conclusions: </strong>GC withdrawal may be feasible in sustained clinically inactive SLE patients. HCQ maintenance can exert a protective role in preventing disease relapse after GC withdrawal. Trial registration number NCT02842814.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"274-283"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370240","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":"Pharmacodynamics of the S1P₁ receptor modulator cenerimod in a phase 2b randomised clinical trial in patients with moderate to severe SLE.","authors":"Madeleine Suffiotti, Pijus Brazauskas, Marcel Peter Keller, Ouali Berkani, Gustavo Seifer, Peter Cornelisse, Mark Joseph Murphy, Daniel Stefan Strasser","doi":"10.1136/ard-2024-226547","DOIUrl":"10.1136/ard-2024-226547","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by autoreactive T and B lymphocytes. Sphingosine-1- phosphate (S1P) is involved in lymphocyte egress from peripheral lymphoid organs into the circulation. In phase 2a clinical trial, the potent, selective S1P₁ receptor modulator cenerimod reduced circulating antibody-secreting cells and interferon (IFN)-associated biomarkers.</p><p><strong>Objectives: </strong>Pharmacodynamic effects of 2 and 4 mg cenerimod were evaluated in the phase 2b clinical trial (CARE) in moderate to severe patients with SLE (NCT03742037).</p><p><strong>Methods: </strong>Blood samples were collected at baseline and after 6 months of treatment with cenerimod or placebo from CARE. The gene expression signatures for type 1 interferon (IFN-1), IFN-γ and plasma cells were used to assess dose-dependent pharmacodynamic effects of cenerimod. Cell-type deconvolution was performed to estimate cell abundance.</p><p><strong>Results: </strong>Cenerimod 4 mg reduced IFN-associated protein and gene signature biomarkers after 6 months compared with placebo. A larger decrease of IFN proteins was evident in IFN-1 high patients compared with IFN-1 low patients. The median IFN-1 score in the IFN-1 high patients was reduced after 6 months of cenerimod 4 mg and the transition from IFN-1 low to high status compared with placebo was prevented. Cenerimod 4 mg exhibited a larger effect size on the pharmacodynamic biomarkers IFN-1, IFN-γ and plasma cells compared with cenerimod 2 mg.</p><p><strong>Conclusions: </strong>This study further characterised the mechanism of action of cenerimod in patients with SLE and substantiated the scientific rationale for cenerimod 4 mg in the phase 3 clinical trials in moderate to severe SLE (OPUS-1/-2).</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"284-293"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370207","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":"Mutilating arthropathy with skin nodules.","authors":"Tsz On Lam, Edric Chi Ching Ip, Wendy Wan Hang Lau, Agnes Wai Sze Chan, Christina Man Tung Cheung, Joshua Jing Xi Li, Joanna Ka Man Ng, Lai-Shan Tam","doi":"10.1136/ard-2024-226186","DOIUrl":"10.1136/ard-2024-226186","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"368-369"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370255","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":"Correction: Olokizumab plus methotrexate: safety and efficacy over 106 weeks of treatment.","authors":"","doi":"10.1136/ard-2023-225473corr1","DOIUrl":"https://doi.org/10.1136/ard-2023-225473corr1","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"373"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370192","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":"ITGA5⁺ synovial fibroblasts orchestrate proinflammatory niche formation by remodelling the local immune microenvironment in rheumatoid arthritis.","authors":"Linli Zheng, Minghui Gu, Xiang Li, Xuantao Hu, Chen Chen, Yunze Kang, Baiqi Pan, Weishen Chen, Guoyan Xian, Xiaoyu Wu, Chengxin Li, Chao Wang, Zhiwen Li, Mingqiang Guan, Guanming Zhou, Ali Mobasheri, Weidong Song, Sui Peng, Puyi Sheng, Ziji Zhang","doi":"10.1136/ard-2024-225778","DOIUrl":"10.1136/ard-2024-225778","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the phenotypic heterogeneity of tissue-resident synovial fibroblasts and their role in inflammatory response in rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>We used single-cell and spatial transcriptomics to profile synovial cells and spatial gene expressions of synovial tissues to identify phenotypic changes in patients with osteoarthritis, RA in sustained remission and active state. Immunohistology, multiplex immunofluorescence and flow cytometry were used to identify synovial fibroblasts subsets. Deconvolution methods further validated our findings in two cohorts (PEAC and R4RA) with treatment response. Cell coculture was used to access the potential cell-cell interactions. Adoptive transfer of synovial cells in collagen-induced arthritis (CIA) mice and bulk RNA sequencing of synovial joints further validate the cellular functions.</p><p><strong>Results: </strong>We identified a novel tissue-remodelling CD45^-CD31^-PDPN⁺ITGA5⁺ synovial fibroblast population with unique transcriptome of POSTN, COL3A1, CCL5 and TGFB1, and enriched in immunoregulatory pathways. This subset was upregulated in active and lympho-myeloid type of RA, associated with an increased risk of multidrug resistance. Transforming growth factor (TGF)-β1 might participate in the differentiation of this subset. Moreover, ITGA5⁺ synovial fibroblasts might occur in early stage of inflammation and induce the differentiation of CXCL13^hiPD^-1^hi peripheral helper T cells (TPHs) from naïve CD4⁺ T cells, by secreting TGF-β1. Intra-articular injection of ITGA5⁺ synovial fibroblasts exacerbates RA development and upregulates TPHs in CIA mice.</p><p><strong>Conclusions: </strong>We demonstrate that ITGA5⁺ synovial fibroblasts might regulate the RA progression by inducing the differentiation of CXCL13^hiPD^-1^hi TPHs and remodelling the proinflammatory microenvironments. Therapeutic modulation of this subpopulation could therefore be a potential treatment strategy for RA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"232-252"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370246","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":"Disease activity of rheumatoid arthritis and kidney function decline: a large prospective registry study.","authors":"Sho Fukui, Wolfgang C Winkelmayer, Sara K Tedeschi, Javier Marrugo, Hongshu Guan, Leslie Harrold, Heather J Litman, Tomohiro Shinozaki, Daniel H Solomon","doi":"10.1136/ard-2024-226156","DOIUrl":"10.1136/ard-2024-226156","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney disease (CKD) is a common comorbidity of rheumatoid arthritis (RA). The association of longitudinal RA disease activity with long-term kidney function has remained uncertain.</p><p><strong>Method: </strong>We analysed a multicentre prospective RA registry in the USA from 2001 to 2022. The exposure was updated time-averaged Clinical Disease Activity Index (TA-CDAI) categories from study enrolment. The primary outcome was a longitudinal estimated glomerular filtration rate (eGFR) change. Secondary outcomes included developments of CKD stage G3a (eGFR<60 mL/min/1.73 m²) and stage G3b (eGFR<45 mL/min/1.73 m²). Results were adjusted for relevant time-fixed and time-varying covariates.</p><p><strong>Results: </strong>31 129 patients (median age: 58.0 years, female: 76.3%, median eGFR: 90.7 mL/min/1.73 m²) contributed 234 973 visits and 146 778 person-years of follow-up. Multivariable mixed-effect linear model showed an average annual eGFR decline during follow-up in the TA-CDAI-remission group of -0.83 mL/min/1.73 m² and estimated additional annual declines (95% CI) of -0.09 (-0.15 to -0.03) in low, -0.17 (-0.23 to -0.10) in moderate and -0.18 (-0.27 to -0.08) mL/min/1.73 m² in high disease activity patients. Compared with TA-CDAI remission, adjusted HRs (95% CI) for CKD stage G3a during follow-up were 1.15 (1.01 to 1.30) in low, 1.22 (1.06 to 1.40) in moderate and 1.27 (1.05 to 1.52) in high disease activity; for CKD stage G3b, 1.22 (0.84 to 1.76) in low, 1.66 (1.12 to 2.45) in moderate and 1.93 (1.16 to 3.20) in high disease activity.</p><p><strong>Conclusions: </strong>Higher RA disease activity was associated with accelerated eGFR decline and increased risk of clinically relevant kidney dysfunction. Future intervention studies should attempt to replicate the association between RA disease activity and eGFR.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"201-209"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psoriatic arthritis phenotype clusters and their association with treatment response: a real-world longitudinal cohort study from the psoriatic arthritis research consortium.","authors":"Paras Karmacharya, Leslie J Crofford, Daniel W Byrne, Alisa Stephens-Shields, M Elaine Husni, Jose U Scher, Ethan Craig, Robert Fitzsimmons, Soumya M Reddy, Marina N Magrey, Jessica A Walsh, Alexis Ogdie","doi":"10.1136/ard-2024-226150","DOIUrl":"10.1136/ard-2024-226150","url":null,"abstract":"<p><strong>Objectives: </strong>To identify phenotype clusters and their trajectories in psoriatic arthritis (PsA) and examine the association of the clusters with treatment response in a real-world setting.</p><p><strong>Methods: </strong>In the multicentre PsA Research Consortium (PARC) study, we applied factor analysis of mixed data to reduce dimensionality and collinearity, followed by hierarchical clustering on principal components. We then evaluated the transition of PsA clusters and their response to new immunomodulatory therapy and tumour necrosis factor inhibitor (TNFi).</p><p><strong>Results: </strong>Among 627 patients with PsA, three clusters were identified: mild PsA and psoriasis only (PsO) (Cluster 1, 47.4%), severe PsA and mild PsO (Cluster 2, 34.3%) and severe PsA and severe PsO (Cluster 3, 18.3%). Among 339 patients starting or changing, significant differences in response were observed (mean follow-up of 0.7 years, SD 0.8), with Cluster 3 showing the largest improvements in cDAPSA and PsAID. No differences were found among those starting TNFi (n=218). cDAPSA remission and PsAID patient acceptable symptom state were achieved in 10% and 54%, respectively. Clusters remained stable over time despite treatment changes, though some transitions occurred, notably from Cluster 3 to milder clusters.</p><p><strong>Conclusion: </strong>Data-driven clusters with distinct therapy responses identified in this real-world study highlight the extensive heterogeneity in PsA and the central role of psoriasis and musculoskeletal severity in treatment outcomes. Concurrently, these findings underscore the need for better outcome measures, particularly for individuals with lower disease activity.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"253-261"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering specific genetic-respiratory disease endotypes for rheumatoid arthritis risk.","authors":"Vanessa L Kronzer, Katrina A Williamson, Keigo Hayashi, Elizabeth J Atkinson, Cynthia S Crowson, Xiaosong Wang, Jing Cui, James R Cerhan, Jennifer A Sletten, Gregory C McDermott, Elena K Joerns, Robert Vassallo, John M Davis, Jeffrey A Sparks","doi":"10.1136/ard-2024-226391","DOIUrl":"10.1136/ard-2024-226391","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to identify specific genetic-respiratory disease endotypes for rheumatoid arthritis (RA) risk.</p><p><strong>Methods: </strong>This case-control study used the Mass General Brigham (MGB) and Mayo Clinic (MC) Biobanks for discovery and replication, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex and health record history. Genetic exposures included the top 11 RA risk alleles, and a validated human leucocyte antigen (HLA) genetic risk score (GRS). We identified seven respiratory diseases by codes. Using logistic regression models adjusting for potential confounders, we estimated Rs with 95% CIs for the interactions between genetic and respiratory exposures for RA risk.</p><p><strong>Results: </strong>We identified 653 RA cases and 2607 controls in MGB, and 428 incident RA cases and 1712 non-RA controls in MC (mean age 64, 69% female). Respiratory diseases were associated with an increased risk of RA (OR 1.34, 95% CI 1.05, 1.71). Six out of 11 non-HLA RA risk alleles interacted strongly with specific respiratory diseases for RA risk, including NFKBIE and sinusitis (OR 5.49, 95% CI 1.56, 19.4 MGB; 5.26, 95% CI 2.00, 13.86 MC) and FAM167A and acute sinusitis for seronegative RA (OR 6.00, 95% CI 2.09, 17.24 MGB; 4.90, 95% CI 1.71, 14.1 MC). The RA HLA GRS interacted synergistically with interstitial lung disease for RA risk (OR 5.41, 95% CI 2.71, 10.8 in MC), with DPB1*02:01, DRB1*16:01 and DRB1*04:04 best predicting RA (positive predictive value 61%).</p><p><strong>Conclusion: </strong>Several genetic-respiratory disease interactions strongly drive RA onset. If confirmed, these novel associations may reflect RA endotypes that can facilitate individualised prevention, diagnosis and treatment.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 2","pages":"221-231"},"PeriodicalIF":20.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}