Arthritis Research & Therapy最新文献

{"title":"Aurora A kinase activation contributes to the fibrotic phenotype in systemic sclerosis through primary cilia shortening.","authors":"Rebecca Wells, Begoña Caballero-Ruiz, Panji Mulipa, Alex J Timmis, Maria E Teves, John Varga, Francesco Del Galdo, Rebecca L Ross, Natalia A Riobo-Del Galdo","doi":"10.1186/s13075-026-03826-6","DOIUrl":"https://doi.org/10.1186/s13075-026-03826-6","url":null,"abstract":"<p><strong>Background: </strong>Systemic sclerosis (SSc) is a severe autoimmune disease characterised by progressive fibrosis driven by fibroblast activation. Primary cilia, key hubs for profibrotic signalling, are markedly shortened in SSc fibroblasts, but the mechanisms underlying this phenotype remain unclear. This study aimed to define the signalling pathways responsible for primary cilia shortening and fibroblast activation in SSc.</p><p><strong>Methods: </strong>Primary dermal fibroblasts from SSc patients and healthy controls were analysed for cilia incidence and length by immunofluorescence, profibrotic marker expression by qPCR, and contractility using gel contraction assays. Cells were treated with TGFβ1 and pharmacological inhibitors targeting AURKA, HDAC6, ROCK2, and Smad3 signalling. CAV1-silenced fibroblasts were used as an in vitro model of SSc.</p><p><strong>Results: </strong>Maintenance of the constitutively short primary cilia phenotype in SSc fibroblasts did not require active TGFβ signalling. However, TGFβ1 induced reversible cilia shortening in healthy fibroblasts and further shortened cilia in SSc fibroblasts to a similar final length, mediated by Rho/ROCK2 rather than canonical Smad3-dependent signalling. Constitutive cilia shortening in SSc was driven by aberrant AURKA activity upstream of HDAC6, promoting ciliary disassembly. Pharmacological inhibition of AURKA or HDAC6 selectively elongated cilia in SSc fibroblasts, reduced profibrotic marker expression, and abrogated fibroblast contractility, but it did not affect healthy control cells. CAV1-silenced fibroblasts similarly exhibited constitutive cilia shortening that was reversed by AURKA inhibition without affecting healthy cells.</p><p><strong>Conclusions: </strong>The AURKA/HDAC6 axis maintains short primary cilia and promotes fibroblast activation in SSc. These findings reveal a mechanistic link between cilia morphology and fibrosis and identify AURKA as a potential therapeutic target for SSc-associated tissue remodelling.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833075","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":"Therapeutic subtypes of knee osteoarthritis: differential treatment effects among predicted endotypes in past clinical trials.","authors":"Monica T Hannani, Peder Frederiksen, Morten A Karsdal, Cecilie L Bager, Asger R Bihlet, Karin Tunblad, Fredrik Öberg, Jamie E Collins, Virginia B Kraus, David J Hunter, Jaume Bacardit, Anne-Christine Bay-Jensen, Christian S Thudium","doi":"10.1186/s13075-026-03825-7","DOIUrl":"https://doi.org/10.1186/s13075-026-03825-7","url":null,"abstract":"<p><strong>Background: </strong>Molecular endotyping may facilitate the successful development of personalized treatments of knee osteoarthritis (KOA). The aim of this exploratory and hypothesis-generating study was to develop a clinically actionable tool for predicting molecular endotypes of KOA using blood-based biomarkers, and to explore the potential for differential treatment effects across biomarker-based endotypes in prior phase II-III KOA drug trials.</p><p><strong>Methods: </strong>Fourteen biomarkers from 226 KOA participants from IMI-APPROACH were assessed for a multinomial logistic regression model to predict structural damage, inflammation, and low tissue turnover endotypes. An optimized panel of six serum biomarkers (C2M, C3M, N-MID, PRO-C2, PRO-C4, sCTX-I) was identified quantitatively by testing all biomarker combinations in models adjusting for age, sex, and BMI. These biomarkers were used for endotype predictions in KOA participants from the randomized placebo-controlled trials MIV-711 (n = 244) (NCT02705625), salmon calcitonin (n = 947) (NCT00486434), and UBX0101 (n = 175) (NCT04129944).</p><p><strong>Results: </strong>The structural damage endotype showed the greatest numerical 26-week reduction in NRS knee pain when treated with MIV-711 (-6.46%; 95% CI: -16.23%, 3.31%). Notably, only the structural damage endotype had a significant two-year reduction in WOMAC pain when treated with salmon calcitonin (-6.19%; 95% CI: -10.55%, -1.83%). Considering the subset treated with salmon calcitonin with the top 20% highest probability of belonging to the structural damage endotype, a 9-15% reduction in standard deviation of the two-year change in WOMAC pain was observed. Enriching the trial for this subset with lower outcome variability could have led to an 18-28% reduction in the needed sample size.</p><p><strong>Conclusions: </strong>This exploratory study suggests the feasibility of predicting KOA endotypes using a minimal panel of tissue-turnover biomarkers. The observed treatment effects of anti-bone resorptive treatments and reduced outcome variability in the structural damage endotype may subtly indicate that aligning treatments with endotypes and drug modes of action can possibly enhance their therapeutic efficacy. Further investigation is needed to establish the true clinical utility of biomarker-based endotyping. Endotype-informed trial design and recruitment may represent a promising strategy to increase the likelihood of success in future KOA clinical trials.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832449","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":"Peripheral blood transcriptomic analysis of patients with rheumatoid arthritis associated interstitial lung disease reveals: distinct molecular signature with evidence of humoral and myeloid immunity.","authors":"Sofia Flouda, Maria Grigoriou, George Sentis, Alexandros Grivas, Nikos Malissovas, Aggelos Banos, Konstantinos Thomas, Noemin Kapsala, Anastasia Filia, Dionysis Nikolopoulos, Theofanis Karageorgas, Vasilios Tzilas, Antonis Fanouriakis, Dimitrios T Boumpas","doi":"10.1186/s13075-026-03767-0","DOIUrl":"https://doi.org/10.1186/s13075-026-03767-0","url":null,"abstract":"<p><strong>Background: </strong>Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in rheumatoid arthritis (RA). RNA sequencing (RNA-seq) of peripheral blood may provide an unbiased look at pathogenetic events involved.</p><p><strong>Methods: </strong>Peripheral blood was collected from RA-ILD (n = 11), RA non-ILD (n = 10), psoriatic arthritis (PsA, n = 23)patients and healthy controls (HC, n = 7) for transcriptomic analysis. All patients in the RA-ILD group were under treatment during sampling, GC and cDMARDs. The gene expression profile of RA ILD was inferred through differential gene expression analysis followed by pathway and enrichment analysis. Further transcriptomic analysis was conducted based on radiological pattern, clinical progression through Modified Medical Research Council (mMRC) Dyspnea scale, and radiological progression. Drug repurposing analysis was performed to identify perturbagens that counteract RA-ILD-specific signatures. To identify shared pathways between SSc and RA we used publicly available RNA-seq data of patients with systemic sclerosis-associated ILD (SSc-ILD).</p><p><strong>Results: </strong>In RA-ILD patients, differential expression analysis revealed enrichment in immune response pathways, metabolism, IFNα and IFNγ response. Within the RA-ILD subgroup, differential expression analysis of clinical and/or radiological progressors versus non-progressors revealed enriched pathways related to cell cycle, DNA replication, IFNγ response, inflammasome assembly and negative regulation of immune response in progressors. Drug repurposing analysis revealed that ITK, Syk and FAK inhibitors are candidate compounds that potentially reverse the transcriptomic signature of RA-ILD progression. Comparison of RA-ILD and SSc revealed shared pathways related to metabolism, extracellular matrix, IFNγ response and response to microorganisms.</p><p><strong>Conclusions: </strong>In this preliminary study, RA-ILD patients exhibit enhanced immune responses, metabolism and cytokine activation. These data need to be further validated in larger studies.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831813","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":"How can innovative trials in juvenile idiopathic arthritis serve the unmet needs of patients?","authors":"Joshua L Bennett, Ethan S Sen, Athimalaipet V Ramanan","doi":"10.1186/s13075-026-03822-w","DOIUrl":"https://doi.org/10.1186/s13075-026-03822-w","url":null,"abstract":"<p><p>Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of childhood-onset inflammatory arthritides that remain challenging to treat. An expanding range of biologic and targeted synthetic disease-modifying antirheumatic drugs has improved outcomes, yet major unmet needs persist including predicting treatment response and identifying optimal drug sequences. Traditional frequentist randomised controlled trials (RCTs) are often infeasible in JIA because of small sample sizes and ethical concerns about placebo use in children. Modified RCTs - including randomised withdrawal, placebo-phase, and escape designs - have reduced placebo exposure but have inherent limitations. Here we discuss how innovative trial methodologies may enhance our capacity to generate evidence that can improve outcomes for children and young people with JIA. Adaptive designs, Bayesian methods, sequential multiple assignment randomized trials, and two-stage stop-go designs offer greater flexibility within trials, allowing for study protocols to be adapted based on preliminary data. Insights from multiomic analysis of JIA synovial tissue mean that biologically defined endotypes may fundamentally reshape trial stratification and support biomarker-led precision medicine. Master protocols (basket, umbrella and platform trials) provide opportunities to streamline research by combining data into a single trial. The incorporation of external data can increase statistical power and circumvent challenges in recruiting paediatric controls. Integrating these methodological and biological innovations will be critical for delivering targeted, effective, and age-inclusive therapeutic strategies, ultimately improving outcomes for children and young people living with JIA.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810091","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":"Factors associated with variations in the 6-minute walk distance during the follow-up of patients with systemic sclerosis.","authors":"Marguerite Merger, Jonathan Giovannelli, David Launay, Nicolas Lamblin, Pascal De Groote, Marie Fertin, Jean-François Bervar, Victor Valentin, Vincent Sobanski, Éric Hachulla, Sébastien Sanges","doi":"10.1186/s13075-026-03821-x","DOIUrl":"https://doi.org/10.1186/s13075-026-03821-x","url":null,"abstract":"<p><strong>Introduction: </strong>The 6-minute walk distance (6MWD) is commonly used to assess functional capacity in patients with systemic sclerosis (SSc), but its ability to reflect changes in cardiopulmonary status during follow-up remains uncertain. This study aimed to investigate whether variations in the 6MWD accurately mirror changes in organ involvement over time in SSc patients.</p><p><strong>Methods: </strong>We conducted a longitudinal study on a global cohort of 227 consecutive SSc patients, including a subgroup of 88 patients with ILD or PH, over a two-year follow-up period. Statistical analyses were performed to assess associations between variations (Δ) of 6MWD (Δ6MWD) and evolution of organ involvement.</p><p><strong>Results: </strong>The 6MWD varied only mildly during follow-up (mean Δ6MWD - 11.6 ± 67.5 m), including in patients with ILD or PH (mean Δ6MWD - 16 ± 74 m). Significant associations were noted between Δ6MWD and variations of several SSc parameters, mostly with modifications in functional status (changes in ΔBorg (ΔΔBorg) score, p = 0.002; ΔNYHA, p < 10^- 3), PH parameters (Δright atrial area, p = 0.045; persistently elevated Nt-pro-BNP levels, p < 10^- 3), chronotropic function (ΔΔheart rate, p = 0.015; Δinitial heart rate, p = 0.024), musculoskeletal involvement (occurrence of joint symptoms, p = 0.006) and perceived quality of life (ΔHAQ-DI score, p = 0.023). In most cases, the strength of these associations was mild to moderate (R² = 0.53, adjusted R² = 0.36 in multivariate analysis), suggesting the influence of additional factors to explain the majority of Δ6MWD.</p><p><strong>Conclusion: </strong>While it remains valuable as a marker of disability and functioning, the variation in the 6MWD does not seem to be a robust surrogate for modifications in organ involvements of SSc patients.</p>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810040","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":"Revisiting osteoarthritis as an inflammatory disease: characterization of synovitis grading and synovial pathotypes in surgical specimens.","authors":"Jacopo Ciaffi, Lorenzo Bianchi, Marco Gambarotti, Alberto Righi, Dilia Giuggioli, Roberto Caporali, Cesare Faldini, Stefano Zaffagnini, Tom W J Huizinga, Francesco Ursini","doi":"10.1186/s13075-026-03819-5","DOIUrl":"https://doi.org/10.1186/s13075-026-03819-5","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760921","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":"Clinical and MRI remission in axial spondyloarthritis: one-year outcomes and predictors from the TRACE treat-to-target study with secukinumab.","authors":"Nora Vladimirova, Mikkel Østergaard, Stylianos Georgiadis, Sengül Seven, Jakob M Møller, Bente Jensen, Rene Østgård, Rene Poggenborg, Ole Rintek Madsen, Oliver Hendricks, Lau Brix, Susanne Juhl Pedersen","doi":"10.1186/s13075-026-03816-8","DOIUrl":"https://doi.org/10.1186/s13075-026-03816-8","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760825","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":"Ultrasound evaluation of muscle quality in rheumatoid arthritis: a reliability study of the Spanish Ultrasound Muscle Assessment in Rheumatoid Arthritis (SpUMAR) score.","authors":"Juan Molina-Collada, José María Bellón, Boris Blanco-Cáceres, Luis Coronel, Juan José de Agustín, Paula Estrada, Elena Garmendia Sánchez, M Luz García Vivar, Otto Olivas-Vergara, Francisco Gabriel Jiménez Núñez, Lucía Mayordomo, Carmen Moragues, Ana Isabel Rebollo-Giménez, Jacqueline Uson, Esther F Vicente-Rabaneda, Esperanza Naredo","doi":"10.1186/s13075-026-03815-9","DOIUrl":"https://doi.org/10.1186/s13075-026-03815-9","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760945","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":"Maternal omega-6 to omega-3 conversion reduces osteoarthritis pain-related behaviors in adult female offspring.","authors":"Arin K Oestreich, Kristin L Lenz, Collin P Murray, Nancy Steward, Sarada Prasad, Sarah K Dunivan, Meredith K Luhmann, Lauryn A Braxton, Farshid Guilak","doi":"10.1186/s13075-026-03817-7","DOIUrl":"https://doi.org/10.1186/s13075-026-03817-7","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760942","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":"Interferon α-induced HERC6 provokes podocyte dysfunction via mitotic catastrophe in lupus nephritis.","authors":"Xiaoquan Wei, Shuhui Wang, Wenkun Peng, Yang Hang, Qianyue Yang, Shuning Sun, Defang Meng, Min Nie, Genhong Yao, Lingyun Sun","doi":"10.1186/s13075-026-03814-w","DOIUrl":"https://doi.org/10.1186/s13075-026-03814-w","url":null,"abstract":"","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760902","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}