Annals of the Rheumatic Diseases最新文献

{"title":"The giant cell arteritis (GCA) ultrasound score (OGUS) at diagnosis and after initial treatment predicts future relapses in GCA patients: results of a multicentre prospective study.","authors":"Sara Monti, Cristina Ponte, Valentin S Schäfer, Davide Rozza, Carlo Scirè, Giulia Franchi, Alessandra Milanesi, Nikita Khmelinskii, Simon M Petzinna, Greta Carrara, Cristina Di Nicola, João Eurico Fonseca, Carlomaurizio Montecucco, Wolfgang A Schmidt, Christian Dejaco, Raashid A Luqmani","doi":"10.1016/j.ard.2025.01.018","DOIUrl":"10.1016/j.ard.2025.01.018","url":null,"abstract":"<p><strong>Objectives: </strong>To test the prognostic role of ultrasonography at diagnosis of giant cell arteritis (GCA) and the change of ultrasound abnormalities during the initial weeks of follow-up for the prediction of relapse, vascular complications, or initiation of disease-modifying antirheumatic drugs (DMARDs).</p><p><strong>Methods: </strong>Prospective, multicentre study of patients with new onset GCA undergoing serial ultrasound assessment at fixed time points. The Outcome Measures in Rheumatology (OMERACT) GCA ultrasonography score (OGUS) was used to quantify vessel wall abnormalities. Relapse was defined as recurrence of GCA-related symptoms or rise of inflammatory markers requiring treatment. A multivariable Poisson model with robust variance estimator was applied, including age, sex, large vessel GCA, glucocorticoid cumulative dose, and baseline OGUS as covariates.</p><p><strong>Results: </strong>Ninety-seven patients were assessed in 849 visits. Thirty-five (36.1%) patients experienced a total of 66 relapses, with median time to relapse of 210 days (IQR, 94.5-323.5). Higher OGUS at diagnosis was associated with an increased risk of relapse within 12 months (incidence rate ratio [IRR] for each 1 point increase in OGUS: 1.85; 95% CI, 1.05-3.32). At multivariable analysis, OGUS normalisation (score <1) over the first 3 weeks was negatively associated with subsequent relapses (IRR, 0.44; 95% CI, 0.22-0.88) and predicted time to first relapse. OGUS reduction over the first 12 weeks was inversely associated with initiation of DMARDs. Ischaemic/aortic complications were rare.</p><p><strong>Conclusions: </strong>Ultrasonography has a prognostic role in GCA and can inform risk stratification. Higher OGUS at diagnosis is associated with relapse, while a higher degree and rapidity of improvement in the first weeks are linked with lower relapse rate.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"823-832"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370130","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":"LLDAS and remission attainment with anifrolumab treatment in patients with systemic lupus erythematosus: results from the TULIP and long-term extension randomised controlled trials.","authors":"Eric F Morand, Ronald van Vollenhoven, Richard A Furie, Kenneth C Kalunian, Susan Manzi, Gabriel Abreu, Raj Tummala, Elizabeth A Duncan, Hussein Al-Mossawi, Catharina Lindholm","doi":"10.1016/j.ard.2025.01.016","DOIUrl":"10.1016/j.ard.2025.01.016","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the long-term impact of anifrolumab versus placebo on lupus low disease activity state (LLDAS) and definition of remission in systemic lupus erythematosus (DORIS) attainment in patients with systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>This post hoc analysis included patients with moderate to severe SLE who were randomly assigned to receive intravenous anifrolumab 300 mg or placebo (once every 4 weeks) in the 52-week, phase 3 TULIP-1/TULIP-2 trials and continued with the same treatment in the 3-year long-term extension. LLDAS/DORIS rates over time were analysed using a stratified Cochran-Mantel-Haenszel approach and logistic regression. Time to first LLDAS/DORIS was estimated using Cox regression. Cumulative time and percentage of time in LLDAS/DORIS were assessed using an analysis of covariance. All P values are nominal.</p><p><strong>Results: </strong>This analysis included 369 patients (anifrolumab n = 257, placebo n = 112). After 4 years of treatment (at Week 208), 36.9% of anifrolumab-treated patients versus 17.1% of placebo-treated patients were in LLDAS (odds ratio [OR], 2.7; 95% CI, 1.3-5.5; P = .0081); 30.3% versus 18.3% were in DORIS (OR, 1.9; 95% CI, 1.0-3.9; P = .0663). Time to first LLDAS and DORIS favoured anifrolumab versus placebo (LLDAS: hazard ratio, 1.56; 95% CI, 1.18-2.09; P = .0024; DORIS: hazard ratio, 1.50; 95% CI, 1.04-2.22; P = .0373). Cumulative time in LLDAS and DORIS was greater with anifrolumab than that with placebo (P = .0004 and P = .0032, respectively).</p><p><strong>Conclusions: </strong>LLDAS and DORIS remission, which are associated with favourable outcomes such as reduced damage and mortality in patients with SLE, are attainable and sustainable treatment targets with long-term anifrolumab treatment.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"777-788"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413004","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":"Efficacy, safety and tolerability of GSK3858279, an anti-CCL17 monoclonal antibody and analgesic, in healthy volunteers and patients with knee osteoarthritis pain: a phase I, randomised, double-blind, placebo-controlled, proof-of-mechanism and proof-of-concept study.","authors":"Jagtar Singh Nijjar, Katharine Abbott-Banner, Yolanda Alvarez, Nicola Aston, Damon Bass, Jane H Bentley, Joanne Ellis, Christian Ellson, Edward C Emery, Maria Feeney, Disala Fernando, David Inman, Rejbinder Kaur, Louise K Modis, Sam Munoz Vicente, Catherine Muya, Kiran Nistala, Eirini Panoilia, Riju Ray, Sarah Siederer, Julia E Smith, Lucinda Weir, Nicolas Wisniacki","doi":"10.1136/ard-2023-225434","DOIUrl":"10.1136/ard-2023-225434","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study was to evaluate efficacy, safety and tolerability of the first-in-class, anti-CCL17 monoclonal antibody, GSK3858279, in treating knee osteoarthritis (OA) pain.</p><p><strong>Methods: </strong>This was a phase I, randomised, placebo-controlled, two-part, proof-of-mechanism and proof-of-concept study. In part A, healthy participants were randomised 3:1 to receive GSK3858279 as either single intravenous (0.1-10 mg/kg) doses, a subcutaneous (3 mg/kg up to 240 mg maximum) dose, or placebo, to evaluate safety and tolerability. In part B, participants with knee OA pain were randomised 1:1 to receive weekly subcutaneous 240 mg GSK3858279, or placebo, for 8 weeks, to assess safety and change from baseline (CFB) in average and worst knee pain intensity. Exploratory endpoints included CFB in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function and stiffness scores.</p><p><strong>Results: </strong>GSK3858279 demonstrated greater median CFB (95% credible interval (CrI)) in average and worst knee pain intensity versus placebo (average, -1.18 (-2.15, -0.20); worst, -1.09 (-2.29, 0.12)) at week 8. Median CFB (95% CrI) for GSK3858279 versus placebo in WOMAC pain and function scores were -1.41 (-2.35, -0.46) and -1.29 (-2.28, -0.29), respectively, at week 8. Overall, 72% (26/36; part A) and 88% (21/24; part B) of participants receiving GSK3858279 experienced adverse events (AEs); with nasopharyngitis being the most common in part A and injection site reactions in part B. No serious AEs or deaths were observed.</p><p><strong>Conclusion: </strong>GSK3858279 improved pain intensity and WOMAC pain and function scores in adults with knee OA pain and demonstrated favourable safety and tolerability in both healthy participants and adults with knee OA pain.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"856-865"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456665","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":"Dysfunctional KLRB1⁺CD8⁺ T-cell responses are generated in chronically inflamed systemic sclerosis skin.","authors":"Alyxzandria M Gaydosik, Tracy Tabib, Jishnu Das, Adriana Larregina, Robert Lafyatis, Patrizia Fuschiotti","doi":"10.1016/j.ard.2025.01.022","DOIUrl":"10.1016/j.ard.2025.01.022","url":null,"abstract":"<p><strong>Objectives: </strong>To analyse the immune mechanisms of diffuse cutaneous systemic sclerosis (dcSSc) skin disease focusing on CD8⁺ T-cell responses in the affected skin of patients because chronic inflammation, vasculopathy, and extensive cutaneous fibrosis are prominent features of dcSSc skin disease, causing pain and disability in patients, with no effective therapy.</p><p><strong>Methods: </strong>Single-cell transcriptomics and epigenomics were applied to well-characterised patient skin samples to identify transcriptomes and key regulators of skin-resident CD8⁺ T-cell subsets. Multicolor immunofluorescence miscoscopy was used to validate molecular findings. Ex vivo skin explant assays were used to functionally characterise dysfunctional CD8⁺ T-cell subsets on nonlesional autologous skin.</p><p><strong>Results: </strong>We identified 2 major developmentally connected CD8⁺ T-cell subpopulations that were expanded in SSc skin lesions compared with healthy control skin. The first was a heterogeneous subset of effector-memory CD8⁺KLRB1⁺IL7R⁺ cells characterised by increased cytolytic and Tc2/Tc17 effector functions that appear to induce tissue damage and fibrosis in early-stage dcSSc skin lesions. The second, found primarily in patients with late-stage disease, was an exhausted CD8⁺KLRG1⁺IL7R^- subset that exhibited transcriptional features of long-lived effector cells, likely contributing to chronic inflammation. Significantly, both subsets were also expanded in other benign dermatoses, implicating these cell populations in the pathogenesis of chronic human skin inflammation.</p><p><strong>Conclusions: </strong>This study provides new insight into core regulatory programmes modulating skin-resident CD8⁺ T-cell plasticity and identifies distinct CD8⁺ T-cell subpopulations that contribute to initiation and chronicity of inflammatory responses in systemic sclerosis skin lesions. These findings reveal prospective molecular targets for new therapeutic strategies against this incurable disease.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"798-809"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078495","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":"Risk of HPV-associated precancer and cancer in women with systemic lupus erythematosus.","authors":"Kanwal Zahid Siddiqi, Louise Baandrup, Louise Diederichsen, Rasmus Hertzum-Larsen, Henrik Christian Bidstrup Leffers, Søren Jacobsen, Susanne Krüger Kjær","doi":"10.1016/j.ard.2025.01.026","DOIUrl":"10.1016/j.ard.2025.01.026","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to compare the occurrence of human papillomavirus (HPV)-associated precancer and cancer in a nationwide cohort of women with systemic lupus erythematosus (SLE) with general female population rates.</p><p><strong>Methods: </strong>In the nationwide Patient Registry, we identified all women in Denmark with a first diagnosis of SLE recorded during 1996-2021 (N = 5092). The cohort was followed up in nationwide registries for HPV-associated precancer and cancer until 2022. Standardised incidence ratios (SIRs) were computed with 95% CIs overall and stratified by age at SLE diagnosis and follow-up time.</p><p><strong>Results: </strong>Compared with general population rates, women with SLE had increased rates of cervical (SIR, 2.3; 95% CI, 2.0-2.7), vaginal (SIR, 4.3; 95% CI, 1.1-9.5), vulvar (SIR, 3.7; 95% CI, 2.3-5.5), and anal (SIR, 4.3; 95% CI, 1.7-8.1) precancers. Increased cancer rates were observed for cervix, anus, and oropharynx, but only the SIR for oropharyngeal cancer was near statistical significance (SIR, 2.5; 95% CI, 0.9-4.9). The increased SIRs for precancers and cancers sustained throughout follow-up and were higher in women diagnosed with SLE at age <50 years compared with ≥50 years, but CIs were overlapping.</p><p><strong>Conclusions: </strong>Women in this nationwide SLE cohort had twice the risk of cervical precancer (vs the general population) and up to 5-fold increased risk of the individual noncervical anogenital precancers. Rates of oropharyngeal cancer and the anogenital cancers were not statistically significantly increased; however, estimates were based on few cases.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"760-766"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073569","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":"GM-CSF drives IL-6 production by macrophages in polymyalgia rheumatica.","authors":"William F Jiemy, Anqi Zhang, Wayel H Abdulahad, Rosanne D Reitsema, Yannick van Sleen, Maria Sandovici, Guillermo Carvajal Alegria, Divi Cornec, Valérie Devauchelle-Pensec, Patrice Hemon, Baptiste Quéré, Sara Boukhlal, Caroline Roozendaal, Thomas Christian Kwee, Bhaskar Dasgupta, Arjan Diepstra, Peter Heeringa, Elisabeth Brouwer, Kornelis S M van der Geest","doi":"10.1016/j.ard.2025.01.004","DOIUrl":"10.1016/j.ard.2025.01.004","url":null,"abstract":"<p><strong>Objectives: </strong>Insight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify the factors driving proinflammatory macrophage development and their functions in the immunopathology of PMR.</p><p><strong>Methods: </strong>Monocyte phenotypes were investigated by flow cytometry in peripheral blood (PMR, n = 22; healthy controls, n = 20) and paired subacromial-subdeltoid (SASD) bursal fluid (PMR, n = 9). Macrophages in SASD bursa were characterised by immunohistochemistry and immunofluorescence (PMR, n = 12; controls undergoing shoulder replacement surgery, n = 10). The functions of cytokines expressed in PMR-affected tissue were examined using macrophage differentiation cultures (PMR, n = 7; healthy controls, n = 7).</p><p><strong>Results: </strong>Monocytes (CD14^highCD16^- and CD14^highCD16⁺) were increased in blood of PMR patients and activated in bursal fluid. Macrophages dominated immune infiltrates in PMR-affected tissue, expressing various proinflammatory cytokines. While interleukin (IL)-6 and interferon-gamma (IFN-γ) expression was abundant in both PMR and control tissue, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) were significantly increased in PMR tissue. Macrophages in PMR-affected tissue showed an elevated CD206/folate receptor β ratio, reflecting a GM-CSF skewed signature. A combination of GM-CSF/M-CSF/IFN-γ significantly boosted IL-6 production in vitro, while limited IL-6 production was observed without GM-CSF.</p><p><strong>Conclusions: </strong>The monocyte compartment is expanded and activated in PMR. Macrophages in PMR-affected tissue produce abundant proinflammatory cytokines such as IL-6. A network of locally expressed cytokines, including GM-CSF, M-CSF, and IFN-γ, may drive the proinflammatory functions of these macrophages. Overall, macrophages may constitute key therapeutic targets for PMR.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"833-843"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363344","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":"Refractory MDA-5 dermatomyositis rapidly progressive interstitial lung disease successfully treated with emapalumab.","authors":"Jennifer Concepcion, Miriam Marti, Susan Vehar, Kelly Corbitt","doi":"10.1016/j.ard.2025.01.010","DOIUrl":"10.1016/j.ard.2025.01.010","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"879-880"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073565","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":"Genetic burden of lupus increases the risk of transition from normal to preclinical autoimmune conditions via antinuclear antibody development.","authors":"Sehwan Chun, So-Young Bang, Ayeong Kwon, Chan Young Kim, Soojin Cha, Young-Chang Kwon, Young Bin Joo, Soo-Kyung Cho, Chan-Bum Choi, Yoon-Kyoung Sung, Ji-Young Han, Tae-Hwan Kim, Jae-Bum Jun, Dae Hyun Yoo, Hye-Soon Lee, Kwangwoo Kim, Sang-Cheol Bae","doi":"10.1016/j.ard.2025.01.015","DOIUrl":"10.1016/j.ard.2025.01.015","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the association between the genetic burden of systemic lupus erythematosus (SLE) and the loss of tolerance to self-nuclear antigens in the preclinical stage.</p><p><strong>Methods: </strong>We analysed genetic data from 349 Korean individuals who tested positive for autoantibodies in the preclinical stage, along with 33,596 healthy controls and 2057 patients with SLE. Genome-wide and pathway-specific polygenic risk scores (PRSs) of SLE were calculated based on 180 known non-human leukocyte antigen (non-HLA) SLE loci, HLA-DRB1 classical alleles, and predefined immune-related pathways to subsequently correlate with clinical phenotypes, particularly the presence of antinuclear antibodies (ANAs) at various titre thresholds.</p><p><strong>Results: </strong>Individuals with preclinical autoimmune conditions exhibited significantly higher SLE PRSs than healthy controls (P = 2.99 × 10^-5), with a significantly upward trend between ANA titres and PRS (P = 1.12 × 10^-3). Stratification analysis revealed that preclinical-stage individuals with PRSs exceeding the means of age- and sex-matched PRSs among patients with SLE were at a significantly higher risk of ANA development (odds ratio = 2.25; P = 8.12 × 10^-3 at a dilution factor of 1:80). Pathway-specific PRS analysis identified the significant enrichment of SLE-risk effects in nine pathways, such as signalling related to reactive oxygen species production, T cell receptor, B cell receptor, and cytokines, in ANA-positive preclinical individuals (P_adjusted < 0.05).</p><p><strong>Conclusions: </strong>Our findings illustrate that the genetic burden of SLE may lead to a crucial transition from normal to preclinical autoimmune conditions prior to the pathogenic stage by increasing the susceptibility to and levels of ANAs.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"789-797"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073554","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":"Molecular endotypes and theratypes in osteoarthritis: transforming a concept into reality with deep learning and multiomics.","authors":"Marie Binvignat, Jérémie Sellam","doi":"10.1016/j.ard.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.ard.2025.03.009","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 5","pages":"657-659"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964783","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":"AI-driven histologic analysis of human Achilles tendinopathy provides a roadmap to unravel pathogenesis.","authors":"Guillaume Planckaert, Arne Burssens, Flore Stappers, Julie Coudenys, Sofía Demolder, Irem Kaya, Malaïka Van der Linden, Amanda Gonçalves, Kelly Lemeire, Benjamin Pavie, Edwin Van Ovost, Peter Burssens, Amber Vanhaecke, Jo Van Dorpe, Lauren Pringels, Evi Wezenbeek, Jess Snedeker, Katrien De Bock, Fiona Bonar, Jill Cook, Jan Victor, Dirk Elewaut, Eric Gracey","doi":"10.1016/j.ard.2025.01.027","DOIUrl":"10.1016/j.ard.2025.01.027","url":null,"abstract":"<p><strong>Objectives: </strong>Achilles tendinopathy is a common source of pain and dysfunction, yet its pathogenesis remains poorly understood. Research on human tendons is hampered by lack of standardisation in tissue sample validation, making interpretation of results challenging. We sought to develop an automated and operator-independent approach to histologically score human tendons.</p><p><strong>Methods: </strong>We assembled a cohort of 15 tendinopathic and 10 normal control Achilles tendon samples. We stained longitudinal sections with haematoxylin and eosin and Alcian blue and developed a low temperature epitope-retrieval protocol for immunostaining of blood vessels. Histologic sections were scored by pathologists using the current gold standard Bonar score. Whole sections were then analysed with open-source software (QuPath). Histologic features were automatically quantified across the entire section and summarised in the BonAIr score. Tissue from the same patients was subsequently analysed by quantitative polymerase chain reaction and flow cytometry to validate elements of the BonAIr score.</p><p><strong>Results: </strong>We observed increased cell roundness, collagen disarrangement, ground substance, and vascularity in tendinopathy using both the Bonar and BonAIr scores. Increased cellularity was only detected by the BonAIr score. Cellular and transcriptomic analyses corroborated tendinopathic shifts in all elements of the BonAIr score and further identified elevated THY1/CD90 expression in tendinopathy. CD90⁺ cells were found to localise to areas of low collagen alignment. These results align with the concept of stromal cell dysregulation in tendinopathy.</p><p><strong>Conclusions: </strong>Automated analysis of whole tendon sections refines conventional histopathologic scoring and predicts cellular and molecular changes found in tendinopathy. The BonAIr score should be further developed for standardised assessment of tendons samples across other anatomical locations and different research centres.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"866-876"},"PeriodicalIF":20.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373756","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}