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
{"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":null,"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<sup>+</sup> 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":""},"PeriodicalIF":20.3000,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of the Rheumatic Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ard.2025.01.027","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍：
Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
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