Pub Date : 2025-11-14DOI: 10.1186/s13075-025-03682-w
Eugen Feist, Michael E. Luggen, Evgeny L. Nasonov, Sergey S. Yakushin, Daria V. Bukhanova, Alina N. Egorova, Sergey A. Grishin, Mikhail Y. Samsonov, Josef S. Smolen
Patients with rheumatoid arthritis (RA) have an increased prevalence of comorbidities, which is associated with higher RA disease activity and worse disease outcomes. The aim of this analysis was to evaluate the impact of the comorbidity burden on the efficacy of the IL-6 inhibitor olokizumab (OKZ) and the tumour necrosis factor (TNF) inhibitor adalimumab (ADA) in the CREDO-2 randomized controlled clinical trial cohort of patients with active RA. A total of 1402 patients with RA were included in the analysis and divided into two groups on the basis of the modified Charlson Comorbidity Index (mCCI) at baseline: those having no comorbid conditions, NCC (mCCI = 1; RA only) vs. those having comorbid conditions, CC (mCCI ≥ 2; RA and ≥ 1 comorbidity). The key outcomes at Week (W) 24 were the proportions of patients with CDAI ≤ 10 and CDAI ≤ 2.8, other outcomes were ACR50 (W12, W24), proportions of patients with SDAI ≤ 3.3 (W24). All groups had similar proportions of approximately 25% of patients with mCCI ≥ 2. There was no significant difference in efficacy between the OKZ q4w or q2w-treated NCC and CC groups at 3 and 6 months of treatment. The same was observed for the placebo group. In contrast, comorbidities reduced CDAI ≤ 10 and ACR50 outcomes upon ADA treatment at 6 months. This post hoc analysis of the phase III CREDO-2 study suggests that the presence of at least one CCI comorbidity, including common disorders such as chronic pulmonary diseases and cardiovascular diseases, does not affect the OKZ treatment results in RA patients. In contrast, comorbidities reduce several efficacy outcomes upon ADA treatment at 6 months. The CCI was not associated with placebo group results and had no influence on safety outcomes. NCT02760407 submitted 2016-05-02.
{"title":"The impact of comorbidities on the efficacy of IL-6 inhibitor olokizumab compared to adalimumab in a randomized controlled trial","authors":"Eugen Feist, Michael E. Luggen, Evgeny L. Nasonov, Sergey S. Yakushin, Daria V. Bukhanova, Alina N. Egorova, Sergey A. Grishin, Mikhail Y. Samsonov, Josef S. Smolen","doi":"10.1186/s13075-025-03682-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03682-w","url":null,"abstract":"Patients with rheumatoid arthritis (RA) have an increased prevalence of comorbidities, which is associated with higher RA disease activity and worse disease outcomes. The aim of this analysis was to evaluate the impact of the comorbidity burden on the efficacy of the IL-6 inhibitor olokizumab (OKZ) and the tumour necrosis factor (TNF) inhibitor adalimumab (ADA) in the CREDO-2 randomized controlled clinical trial cohort of patients with active RA. A total of 1402 patients with RA were included in the analysis and divided into two groups on the basis of the modified Charlson Comorbidity Index (mCCI) at baseline: those having no comorbid conditions, NCC (mCCI = 1; RA only) vs. those having comorbid conditions, CC (mCCI ≥ 2; RA and ≥ 1 comorbidity). The key outcomes at Week (W) 24 were the proportions of patients with CDAI ≤ 10 and CDAI ≤ 2.8, other outcomes were ACR50 (W12, W24), proportions of patients with SDAI ≤ 3.3 (W24). All groups had similar proportions of approximately 25% of patients with mCCI ≥ 2. There was no significant difference in efficacy between the OKZ q4w or q2w-treated NCC and CC groups at 3 and 6 months of treatment. The same was observed for the placebo group. In contrast, comorbidities reduced CDAI ≤ 10 and ACR50 outcomes upon ADA treatment at 6 months. This post hoc analysis of the phase III CREDO-2 study suggests that the presence of at least one CCI comorbidity, including common disorders such as chronic pulmonary diseases and cardiovascular diseases, does not affect the OKZ treatment results in RA patients. In contrast, comorbidities reduce several efficacy outcomes upon ADA treatment at 6 months. The CCI was not associated with placebo group results and had no influence on safety outcomes. NCT02760407 submitted 2016-05-02.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"87 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515651","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}
Pub Date : 2025-11-14DOI: 10.1186/s13075-025-03665-x
Kalliopi Klavdianou, Daniel Benjamin Abrar, Alexander Dieter Mewes, Styliani Tsiami, Philipp Sewerin, Xenofon Baraliakos
Radiography is commonly used in clinical practice for detecting syndesmophytes in radiographic axial Spondyloarthritis (r-axSpA), while the ability of magnetic resonance imaging (MRI) to detect such bony structures is questionable due to its slicing technique. We aimed to assess the ability and performance for detection of syndesmophytes on MRI using different slice thicknesses and compare them with radiography in r-axSpA. MRI (T1-weighted (T1W) sequences) with slice thicknesses of 1–6 mm of the lower thoracic and lumbar spine were prospectively performed in patients with available radiographs. Each vertebral corner (VC) (anterior and posterior) from thoracic (Th11) to lumbar (L5) was assessed for presence/absence of syndesmophytes and/or fat lesions (FL, MRI only) by two experienced readers in independent MRI and radiography sessions and agreement was then reached in consensus. A total of 1.204 VCs were assessed from 43 r-axSpA patients. Syndesmophytes were recorded in 19.3% VCs on radiography and in 38.3%, 37.5%, 34.8%, 33.7%, 31.4%, 28.7% VCs on MRI slice thicknesses of 1–6 mm, respectively (all p ≤ 0.001 vs. radiography). Although more syndesmophytes were recorded on MRI than radiography, MRI also missed 21%-31.3% syndesmophytes detected in radiography. Agreement with radiography was found in 72.6%, 73.8%, 75.9%, 76%, 77.3% and 78.5% on MRI slice thicknesses of 1–6 mm, respectively. FL were detected in 38.2%-39.2% in slice thicknesses 1–6 mm. Occurrence of FL was associated with better agreement between MRI and radiography findings. The thinner the MRI slices, the more syndesmophytes were detected compared to radiography, but the best agreement with radiography was found in the thicker slices. The presence of fat lesions on MRI was associated with better agreement with radiography for syndesmophyte detection.
{"title":"The impact of MRI slice thickness on the detection of spinal syndesmophytes in axial spondyloarthritis","authors":"Kalliopi Klavdianou, Daniel Benjamin Abrar, Alexander Dieter Mewes, Styliani Tsiami, Philipp Sewerin, Xenofon Baraliakos","doi":"10.1186/s13075-025-03665-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03665-x","url":null,"abstract":"Radiography is commonly used in clinical practice for detecting syndesmophytes in radiographic axial Spondyloarthritis (r-axSpA), while the ability of magnetic resonance imaging (MRI) to detect such bony structures is questionable due to its slicing technique. We aimed to assess the ability and performance for detection of syndesmophytes on MRI using different slice thicknesses and compare them with radiography in r-axSpA. MRI (T1-weighted (T1W) sequences) with slice thicknesses of 1–6 mm of the lower thoracic and lumbar spine were prospectively performed in patients with available radiographs. Each vertebral corner (VC) (anterior and posterior) from thoracic (Th11) to lumbar (L5) was assessed for presence/absence of syndesmophytes and/or fat lesions (FL, MRI only) by two experienced readers in independent MRI and radiography sessions and agreement was then reached in consensus. A total of 1.204 VCs were assessed from 43 r-axSpA patients. Syndesmophytes were recorded in 19.3% VCs on radiography and in 38.3%, 37.5%, 34.8%, 33.7%, 31.4%, 28.7% VCs on MRI slice thicknesses of 1–6 mm, respectively (all p ≤ 0.001 vs. radiography). Although more syndesmophytes were recorded on MRI than radiography, MRI also missed 21%-31.3% syndesmophytes detected in radiography. Agreement with radiography was found in 72.6%, 73.8%, 75.9%, 76%, 77.3% and 78.5% on MRI slice thicknesses of 1–6 mm, respectively. FL were detected in 38.2%-39.2% in slice thicknesses 1–6 mm. Occurrence of FL was associated with better agreement between MRI and radiography findings. The thinner the MRI slices, the more syndesmophytes were detected compared to radiography, but the best agreement with radiography was found in the thicker slices. The presence of fat lesions on MRI was associated with better agreement with radiography for syndesmophyte detection.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"143 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516218","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}
Pub Date : 2025-11-13DOI: 10.1186/s13075-025-03681-x
Shoubin Zhan, Zhongyu Wang, Ye Xu, Shengkai Zhou, Minghui Ge, Yunjie Song, Yi Zhu, Huan Dou, Han Shen, Ping Yang
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by dysregulated inflammatory response lacking reliable diagnosis biomarkers and therapy targets. Extracellular vesicles (EVs)-derived cargo as biomarkers and mediators of SLE have garnered significant attention, however, quantitative inflammatory protein profile of SLE EVs remain uncovered. Current study focuses on exploring the inflammatory protein landscape of SLE serum EVs via quantitative proximity extension assay (PEA) and evaluates their diagnostic utility for SLE and lupus nephritis (LN). In this cross-sectional study, we first utilized PEA to profile inflammatory proteins derived from serum EVs in 101 individuals, including 70 SLE patients and 33 healthy controls (HCs). Subsequently, candidate EV proteins identified from this analysis were subsequently validated via ELISA in an independent cohort comprising 54 SLE patients and 58 HCs. Furthermore, machine-learning classification was utilized to generate prediction models for SLE diagnosis and LN discrimination. Finally, correlation analysis was applied to evaluate the association between EV-derived inflammatory proteins and clinical parameters. In the sEV PEA discovery cohort, a total of 49 significantly dysregulated inflammatory proteins with 43 elevated proteins were identified in serum EVs from SLE patients. Two precision prediction models were generated using the random Forest algorithm (RF) for SLE identification and LN discrimination, achieving AUCs of 0.999 and 0.793, respectively. Multiple EV proteins such as CCL23, IL-18R1, SCF and CSF-1 showed a significant correlation with SLE severity parameters including SLEDAI, eGFR and UACR. Furthermore, representative EV proteins including IL-18R1, CCL23 and IFN-γ were further tested in the sEV ELISA validation cohort including 54 SLE patients and 58 HCs. The present study identified a unique pattern EV-derived inflammatory proteins in patients with SLE, which could serve as novel biomarkers for SLE diagnosis and disease monitoring.
{"title":"Inflammation-related proteomics of extracellular vesicles as novel biomarkers for systemic lupus erythematosus revealed by proximity extension assay","authors":"Shoubin Zhan, Zhongyu Wang, Ye Xu, Shengkai Zhou, Minghui Ge, Yunjie Song, Yi Zhu, Huan Dou, Han Shen, Ping Yang","doi":"10.1186/s13075-025-03681-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03681-x","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by dysregulated inflammatory response lacking reliable diagnosis biomarkers and therapy targets. Extracellular vesicles (EVs)-derived cargo as biomarkers and mediators of SLE have garnered significant attention, however, quantitative inflammatory protein profile of SLE EVs remain uncovered. Current study focuses on exploring the inflammatory protein landscape of SLE serum EVs via quantitative proximity extension assay (PEA) and evaluates their diagnostic utility for SLE and lupus nephritis (LN). In this cross-sectional study, we first utilized PEA to profile inflammatory proteins derived from serum EVs in 101 individuals, including 70 SLE patients and 33 healthy controls (HCs). Subsequently, candidate EV proteins identified from this analysis were subsequently validated via ELISA in an independent cohort comprising 54 SLE patients and 58 HCs. Furthermore, machine-learning classification was utilized to generate prediction models for SLE diagnosis and LN discrimination. Finally, correlation analysis was applied to evaluate the association between EV-derived inflammatory proteins and clinical parameters. In the sEV PEA discovery cohort, a total of 49 significantly dysregulated inflammatory proteins with 43 elevated proteins were identified in serum EVs from SLE patients. Two precision prediction models were generated using the random Forest algorithm (RF) for SLE identification and LN discrimination, achieving AUCs of 0.999 and 0.793, respectively. Multiple EV proteins such as CCL23, IL-18R1, SCF and CSF-1 showed a significant correlation with SLE severity parameters including SLEDAI, eGFR and UACR. Furthermore, representative EV proteins including IL-18R1, CCL23 and IFN-γ were further tested in the sEV ELISA validation cohort including 54 SLE patients and 58 HCs. The present study identified a unique pattern EV-derived inflammatory proteins in patients with SLE, which could serve as novel biomarkers for SLE diagnosis and disease monitoring.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"36 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499414","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}
Pub Date : 2025-11-13DOI: 10.1186/s13075-025-03662-0
Hao Cheng Shen, Océane Landon-Cardinal, Josiane Bourré-Tessier, Sabrina Hoa, Farah Zarka, Jessica Nehme, Anne-Marie Mansour, Jean-Paul Makhzoum, Alexandra Mereniuk, Rosalie-Sélène Meunier, Maude Bouchard-Marmen, Laurence Poirier-Blanchette, Marianne Landry, Marianne Lévesque, Rami Massie, Oliver Blanchard, Fredéric Lefebvre, Jean-Richard Goulet, Eric Rich, Jean-Pierre Raynauld, Gemma Pérez, Martial Koenig, Hugues Allard-Chamard, Julie Drouin, Sandra Chartrand, Michelle Aaron, Victoria Ivensky, Maria Infantino, Margherita Giannini, Zoe Betteridge, Valérie Leclair, Marie Hudson, Jason Karamchandani, Baptiste Hervier, Erin O’Ferrall, Benjamin Ellezam, Ira N. Targoff, Minoru Satoh, Marvin J. Fritzler, Jean-Luc Senécal, Alain Meyer, Yves Troyanov
To explore the link between moderate to severe oropharyngeal dysphagia and cancer in autoimmune myositis (AIM) other than inclusion body myositis (IBM). The medical records of patients with AIM seen in rheumatology in two university hospitals from January 2000 to December 2022 were retrospectively reviewed. Using an updated AIM subclassification, patients were classified by expert opinion as pure dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), scleromyositis, lupomyositis, anti-MDA-5 syndrome, antisynthetase syndrome (ASyS) or polymyositis syndrome. Objective oropharyngeal dysphagia at myositis diagnosis was defined by an abnormal videofluoroscopic swallowing study and/or the need for percutaneous gastrojejunostomy. The presence of cancer within 3 years of myositis diagnosis was recorded. Pure DM accounted for 50% (n = 20/40) of the cases of objective oropharyngeal dysphagia, while anti-MDA-5 syndrome and ASyS together represented 8% (n = 3/40). Cancers occurred predominantly in pure DM (n = 27/33), and rarely in scleromyositis (n = 1/53), anti-MDA-5 syndrome and ASyS (n = 0/62). Among patients 50 years of age or older with pure DM (n = 50), cancer was present in 40% (n = 4/10) of patients with no muscle weakness, 45% (n = 10/22) in those with proximal weakness alone, 44% (n = 4/9) in those with moderate dysphagia and 100% of those with severe dysphagia (n = 9/9) (p = 0.02 by two-sided Fisher’s exact test). Recognizing scleromyositis, anti-MDA-5 and ASyS as distinct from pure DM improves risk stratification for cancer screening. In patients ≥ 50 years with pure DM, severe oropharyngeal dysphagia is strongly associated with cancer, suggesting a paraneoplastic myopathy with an ineffective anticancer immune response.
{"title":"Revisiting the link between oropharyngeal dysphagia and cancer in autoimmune myositis: a descriptive study","authors":"Hao Cheng Shen, Océane Landon-Cardinal, Josiane Bourré-Tessier, Sabrina Hoa, Farah Zarka, Jessica Nehme, Anne-Marie Mansour, Jean-Paul Makhzoum, Alexandra Mereniuk, Rosalie-Sélène Meunier, Maude Bouchard-Marmen, Laurence Poirier-Blanchette, Marianne Landry, Marianne Lévesque, Rami Massie, Oliver Blanchard, Fredéric Lefebvre, Jean-Richard Goulet, Eric Rich, Jean-Pierre Raynauld, Gemma Pérez, Martial Koenig, Hugues Allard-Chamard, Julie Drouin, Sandra Chartrand, Michelle Aaron, Victoria Ivensky, Maria Infantino, Margherita Giannini, Zoe Betteridge, Valérie Leclair, Marie Hudson, Jason Karamchandani, Baptiste Hervier, Erin O’Ferrall, Benjamin Ellezam, Ira N. Targoff, Minoru Satoh, Marvin J. Fritzler, Jean-Luc Senécal, Alain Meyer, Yves Troyanov","doi":"10.1186/s13075-025-03662-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03662-0","url":null,"abstract":"To explore the link between moderate to severe oropharyngeal dysphagia and cancer in autoimmune myositis (AIM) other than inclusion body myositis (IBM). The medical records of patients with AIM seen in rheumatology in two university hospitals from January 2000 to December 2022 were retrospectively reviewed. Using an updated AIM subclassification, patients were classified by expert opinion as pure dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), scleromyositis, lupomyositis, anti-MDA-5 syndrome, antisynthetase syndrome (ASyS) or polymyositis syndrome. Objective oropharyngeal dysphagia at myositis diagnosis was defined by an abnormal videofluoroscopic swallowing study and/or the need for percutaneous gastrojejunostomy. The presence of cancer within 3 years of myositis diagnosis was recorded. Pure DM accounted for 50% (n = 20/40) of the cases of objective oropharyngeal dysphagia, while anti-MDA-5 syndrome and ASyS together represented 8% (n = 3/40). Cancers occurred predominantly in pure DM (n = 27/33), and rarely in scleromyositis (n = 1/53), anti-MDA-5 syndrome and ASyS (n = 0/62). Among patients 50 years of age or older with pure DM (n = 50), cancer was present in 40% (n = 4/10) of patients with no muscle weakness, 45% (n = 10/22) in those with proximal weakness alone, 44% (n = 4/9) in those with moderate dysphagia and 100% of those with severe dysphagia (n = 9/9) (p = 0.02 by two-sided Fisher’s exact test). Recognizing scleromyositis, anti-MDA-5 and ASyS as distinct from pure DM improves risk stratification for cancer screening. In patients ≥ 50 years with pure DM, severe oropharyngeal dysphagia is strongly associated with cancer, suggesting a paraneoplastic myopathy with an ineffective anticancer immune response. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145499440","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}
Pub Date : 2025-11-11DOI: 10.1186/s13075-025-03673-x
Kexin Xu, Taotao Li, Na Gao, Yaxin Zhang, Yi Yang, Honglei Zhao, Longfei Wang, Junming Zhu, Jian Liu, Lili Pan
Takayasu arteritis (TAK) is a rare, chronic large-vessel vasculitis. Although CD4⁺ and CD8⁺ T cells are acknowledged drivers of vascular injury in TAK, the gene networks that confer their pathogenicity remain incompletely mapped. This study aimed to integrate bulk RNA-sequencing of peripheral-blood T-cell subsets with single-cell RNA-sequencing of aortic tissue to find mechanistic biomarkers and therapeutic targets for TAK. We performed bulk RNA-sequencing on peripheral-blood CD4⁺ and CD8⁺ T cells from eight treatment-naïve TAK patients and three age matched healthy controls. In parallel, single-cell RNA-sequencing was applied to aortic tissue from three additional TAK patients and three atherosclerotic controls. DEGs were defined at false-discovery rate < 0.05. Functional enrichment used Gene Ontology, KEGG and Reactome. STRING constructed protein–protein interaction networks, and Cell Chat inferred intercellular ligand–receptor communication. Bulk profiling identified 851 DEGs in CD4⁺ and 1 645 DEGs in CD8⁺ T cells. CD4⁺ DEGs were enriched for inflammation, angiogenesis and platelet-activation pathways; CD8⁺ DEGs concentrated on cytokine synthesis, notably interleukin-1 signaling. Both subsets shared enrichment in complement cascade, focal adhesion and extracellular-matrix organization, indicating convergent pro-inflammatory programs. Single-cell analyses delineated dense CD4⁺– CD8⁺ crosstalk within TAK aorta and, relative to atherosclerotic controls, heat-shock protein binding and ubiquitin-ligase activity—hallmarks of heightened protein-homeostasis stress. Four transcriptional regulators—EGR1, KLF4, RHOB and ATF3—were consistently up-regulated in both blood and tissue; EGR1 showed the strongest fold-change and occupied a central hub in protein-interaction and ligand–receptor networks. In peripheral cells EGR1 co-clustered with cytokine-biosynthetic modules, while in tissue its profile mirrored the composite CD4⁺ and CD8⁺ signature, underscoring a unifying role in systemic and local inflammation. Integrated bulk and single-cell transcriptomics reveal both shared and subset-specific signaling landscapes for CD4⁺ and CD8⁺ T cells in TAK. The consistent prominence of EGR1 across compartments nominates this factor as a pivotal molecular switch and attractive therapeutic target. These data furnish a mechanistic framework for precision immune modulation in large-vessel vasculitis.
{"title":"Integrated bulk and single-cell transcriptomics identifies shared and specific immune signatures in Takayasu Arteritis","authors":"Kexin Xu, Taotao Li, Na Gao, Yaxin Zhang, Yi Yang, Honglei Zhao, Longfei Wang, Junming Zhu, Jian Liu, Lili Pan","doi":"10.1186/s13075-025-03673-x","DOIUrl":"https://doi.org/10.1186/s13075-025-03673-x","url":null,"abstract":"Takayasu arteritis (TAK) is a rare, chronic large-vessel vasculitis. Although CD4⁺ and CD8⁺ T cells are acknowledged drivers of vascular injury in TAK, the gene networks that confer their pathogenicity remain incompletely mapped. This study aimed to integrate bulk RNA-sequencing of peripheral-blood T-cell subsets with single-cell RNA-sequencing of aortic tissue to find mechanistic biomarkers and therapeutic targets for TAK. We performed bulk RNA-sequencing on peripheral-blood CD4⁺ and CD8⁺ T cells from eight treatment-naïve TAK patients and three age matched healthy controls. In parallel, single-cell RNA-sequencing was applied to aortic tissue from three additional TAK patients and three atherosclerotic controls. DEGs were defined at false-discovery rate < 0.05. Functional enrichment used Gene Ontology, KEGG and Reactome. STRING constructed protein–protein interaction networks, and Cell Chat inferred intercellular ligand–receptor communication. Bulk profiling identified 851 DEGs in CD4⁺ and 1 645 DEGs in CD8⁺ T cells. CD4⁺ DEGs were enriched for inflammation, angiogenesis and platelet-activation pathways; CD8⁺ DEGs concentrated on cytokine synthesis, notably interleukin-1 signaling. Both subsets shared enrichment in complement cascade, focal adhesion and extracellular-matrix organization, indicating convergent pro-inflammatory programs. Single-cell analyses delineated dense CD4⁺– CD8⁺ crosstalk within TAK aorta and, relative to atherosclerotic controls, heat-shock protein binding and ubiquitin-ligase activity—hallmarks of heightened protein-homeostasis stress. Four transcriptional regulators—EGR1, KLF4, RHOB and ATF3—were consistently up-regulated in both blood and tissue; EGR1 showed the strongest fold-change and occupied a central hub in protein-interaction and ligand–receptor networks. In peripheral cells EGR1 co-clustered with cytokine-biosynthetic modules, while in tissue its profile mirrored the composite CD4⁺ and CD8⁺ signature, underscoring a unifying role in systemic and local inflammation. Integrated bulk and single-cell transcriptomics reveal both shared and subset-specific signaling landscapes for CD4⁺ and CD8⁺ T cells in TAK. The consistent prominence of EGR1 across compartments nominates this factor as a pivotal molecular switch and attractive therapeutic target. These data furnish a mechanistic framework for precision immune modulation in large-vessel vasculitis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"90 1","pages":"209"},"PeriodicalIF":4.9,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145492578","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}
Pub Date : 2025-11-06DOI: 10.1186/s13075-025-03674-w
Kinga Fritsch, Judit Majnik, Michal Tomčík, Janos Gyebnar, Tamas Munkacsi, Hanna Balogh, Tamas Purczel, Pal Maurovich-Horvat, Tamas Nagy, Alexandra Nagy, Veronika Muller, Nikolett Marton, Gyorgy Nagy
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major contributor to rheumatoid arthritis (RA) related morbidity and mortality. Early detection is challenging due to subclinical onset and limitations of conventional screening modalities. This study evaluated the diagnostic performance of low-dose photon-counting detector CT (LD PCD-CT) for RA-ILD and assessed its prevalence and risk factors in a Hungarian RA cohort. In this prospective study (Feb 2022–June 2023), 492 consecutively enrolled RA patients without known ILD, underwent LD PCD-CT, digital chest radiography (DR) and pulmonary function testing (PFTs). Imaging was scored using a standardized LD severity scale. Clinical, demographic, and serological data were analyzed to identify ILD predictors. Statistical analyses included Kolmogorov–Smirnov, t-tests, Mann–Whitney U, chi-squared/Fisher’s exact tests, Pearson correlation, and ROC analysis. Logistic regression was used to identify independent risk factors. LD PCD-CT identified interstitial abnormalities in 35% of patients. By contrast, clinical assessment and PFTs detected abnormalities in only 44% and 22% of these cases, respectively. Among patients without CT-defined abnormalities, 42% had a positive clinical assessment and 23% had abnormal PFTs, indicating limited diagnostic specificity. The most frequent findings were interstitial reticular abnormalities (58%) and usual interstitial pneumonia (22%). Independent ILD predictors included age ≥ 50 years, male sex, ≥ 25 pack-year smoking history, rheumatoid factor (RF) positivity, and elevated lactate dehydrogenase (LDH) levels. LD PCD-CT had a mean effective radiation dose of 0.415 mSv, remaining within low-dose diagnostic thresholds. LD PCD-CT demonstrated superior sensitivity and specificity for early RA-ILD detection compared to clinical assessment and PFTs, while maintaining low radiation exposure. Incorporating LD PCD-CT into risk-stratified screening protocols may facilitate earlier diagnosis and timely therapeutic interventions, ultimately improving patient outcomes. NCT05391100.
{"title":"Screening for rheumatoid arthritis-associated interstitial lung disease using low-dose CT: an emerging approach — an observational prospective case-control study","authors":"Kinga Fritsch, Judit Majnik, Michal Tomčík, Janos Gyebnar, Tamas Munkacsi, Hanna Balogh, Tamas Purczel, Pal Maurovich-Horvat, Tamas Nagy, Alexandra Nagy, Veronika Muller, Nikolett Marton, Gyorgy Nagy","doi":"10.1186/s13075-025-03674-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03674-w","url":null,"abstract":"Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major contributor to rheumatoid arthritis (RA) related morbidity and mortality. Early detection is challenging due to subclinical onset and limitations of conventional screening modalities. This study evaluated the diagnostic performance of low-dose photon-counting detector CT (LD PCD-CT) for RA-ILD and assessed its prevalence and risk factors in a Hungarian RA cohort. In this prospective study (Feb 2022–June 2023), 492 consecutively enrolled RA patients without known ILD, underwent LD PCD-CT, digital chest radiography (DR) and pulmonary function testing (PFTs). Imaging was scored using a standardized LD severity scale. Clinical, demographic, and serological data were analyzed to identify ILD predictors. Statistical analyses included Kolmogorov–Smirnov, t-tests, Mann–Whitney U, chi-squared/Fisher’s exact tests, Pearson correlation, and ROC analysis. Logistic regression was used to identify independent risk factors. LD PCD-CT identified interstitial abnormalities in 35% of patients. By contrast, clinical assessment and PFTs detected abnormalities in only 44% and 22% of these cases, respectively. Among patients without CT-defined abnormalities, 42% had a positive clinical assessment and 23% had abnormal PFTs, indicating limited diagnostic specificity. The most frequent findings were interstitial reticular abnormalities (58%) and usual interstitial pneumonia (22%). Independent ILD predictors included age ≥ 50 years, male sex, ≥ 25 pack-year smoking history, rheumatoid factor (RF) positivity, and elevated lactate dehydrogenase (LDH) levels. LD PCD-CT had a mean effective radiation dose of 0.415 mSv, remaining within low-dose diagnostic thresholds. LD PCD-CT demonstrated superior sensitivity and specificity for early RA-ILD detection compared to clinical assessment and PFTs, while maintaining low radiation exposure. Incorporating LD PCD-CT into risk-stratified screening protocols may facilitate earlier diagnosis and timely therapeutic interventions, ultimately improving patient outcomes. NCT05391100. ","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"19 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447174","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}
Pub Date : 2025-11-05DOI: 10.1186/s13075-025-03638-0
Ihsan Hammoura, Renée H. Fiechter, Leonieke J. J. van Mens, Henriëtte M. Y. de Jong, Inka A. Fluri, Sander W. Tas, Dominique L.P. Baeten, Marleen G.H. van de Sande, Nataliya G. Yeremenko
IL-17 A plays a role in the pathology of spondyloarthritis (SpA), as evidenced by the clinical efficacy of IL-17 A inhibitors (IL-17Ai). Nevertheless, the exact role of IL-17 A in driving synovial inflammation and pathological remodeling remains unknown. In this study, we investigated the molecular pathways affected by IL-17Ai in SpA synovitis to determine whether this response is tissue- and/or treatment-specific. Synovial biopsies from 12 peripheral SpA (pSpA) patients before and after 12 weeks of IL-17Ai treatment were analyzed by RNA-sequencing and qPCRs. The synovial tissue response to IL-17Ai in 7 psoriatic arthritis (PsA) patients was compared to open-source gene expression data of skin biopsies from 15 psoriasis (PsO) patients treated with IL-17Ai, and synovial biopsies from 7 PsA patients receiving IL-12p40/IL-23p40 blockade. Compared to baseline, IL-17Ai significantly modulated the expression of 1255 genes (549 upregulated and 706 downregulated, FDR < 0.1) in the synovium at week 12. The downregulated genes were predominantly associated with inflammatory processes and stromal functions. Comprehensive analysis revealed that IL-17Ai-mediated suppression of bone remodeling is independent of its inhibition of inflammatory pathways. While IL-17Ai consistently attenuated inflammation-related pathways in both psoriatic joints and skin, its effect on bone remodeling pathways was specific to the synovium. This distinguishes IL-17Ai from IL-12p40/IL-23p40 inhibitors, which, while mitigating synovial inflammation, did not affect tissue remodeling. Our findings provide new insights into the molecular mechanisms of IL-17 A blockade in pSpA, underscoring its unique role in selectively targeting bone-remodeling processes specific to the joints of individuals with SpA.
{"title":"Dual impact of interleukin-17 A blockade on inflammatory and stromal pathways in peripheral spondyloarthritis","authors":"Ihsan Hammoura, Renée H. Fiechter, Leonieke J. J. van Mens, Henriëtte M. Y. de Jong, Inka A. Fluri, Sander W. Tas, Dominique L.P. Baeten, Marleen G.H. van de Sande, Nataliya G. Yeremenko","doi":"10.1186/s13075-025-03638-0","DOIUrl":"https://doi.org/10.1186/s13075-025-03638-0","url":null,"abstract":"IL-17 A plays a role in the pathology of spondyloarthritis (SpA), as evidenced by the clinical efficacy of IL-17 A inhibitors (IL-17Ai). Nevertheless, the exact role of IL-17 A in driving synovial inflammation and pathological remodeling remains unknown. In this study, we investigated the molecular pathways affected by IL-17Ai in SpA synovitis to determine whether this response is tissue- and/or treatment-specific. Synovial biopsies from 12 peripheral SpA (pSpA) patients before and after 12 weeks of IL-17Ai treatment were analyzed by RNA-sequencing and qPCRs. The synovial tissue response to IL-17Ai in 7 psoriatic arthritis (PsA) patients was compared to open-source gene expression data of skin biopsies from 15 psoriasis (PsO) patients treated with IL-17Ai, and synovial biopsies from 7 PsA patients receiving IL-12p40/IL-23p40 blockade. Compared to baseline, IL-17Ai significantly modulated the expression of 1255 genes (549 upregulated and 706 downregulated, FDR < 0.1) in the synovium at week 12. The downregulated genes were predominantly associated with inflammatory processes and stromal functions. Comprehensive analysis revealed that IL-17Ai-mediated suppression of bone remodeling is independent of its inhibition of inflammatory pathways. While IL-17Ai consistently attenuated inflammation-related pathways in both psoriatic joints and skin, its effect on bone remodeling pathways was specific to the synovium. This distinguishes IL-17Ai from IL-12p40/IL-23p40 inhibitors, which, while mitigating synovial inflammation, did not affect tissue remodeling. Our findings provide new insights into the molecular mechanisms of IL-17 A blockade in pSpA, underscoring its unique role in selectively targeting bone-remodeling processes specific to the joints of individuals with SpA.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"91 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145441235","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}
Pub Date : 2025-11-05DOI: 10.1186/s13075-025-03648-y
Oliver O’Sullivan, Ana M. Valdes, Fraje Watson, Stefan Kluzek, Anthony M. J. Bull, Alexander N. Bennett
Post-traumatic osteoarthritis (PTOA) is a complex condition with multiple pathological processes at play. Molecular biomarkers can enable a better understanding of these processes, thus enhancing case endotyping, phenotyping, personalised care and drug discovery. The longitudinal ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) study offers the opportunity to develop insights into PTOA pathophysiology using a panel of extra-cellular matrix turnover, inflammatory and metabolic biomarkers and their cross-sectional (associative) and longitudinal (predictive) relationship to features of radiographic PTOA in a cohort of young, male, severely injured servicepersonnel. Using serum and radiographic data gathered in the baseline (8-years) and first follow-up visit (11-years) post-injury of ADVANCE (n = 1145), two analyses were undertaken. Firstly, cross-sectional univariate analysis between serum COMP, CTX-II, PIIANP, IL-1b, IL-17a, TNF-a, leptin and adiponectin and radiographic features (joint space narrowing (JSN), osteophytes and sclerosis), followed by the longitudinal prediction of new or progression of these three radiographic features using LASSO to select predictors. The area under a ROC curve (AUROC) was computed. Complete radiographic and serum case data in n = 872 male British servicemen, aged 34.5 (5.5) at baseline and 38.3 (5.4) at follow-up were analysed. Those with JSN had significantly higher concentrations of leptin (FDR-corrected q-value, q = 0.04). COMP had an AUROC of 0.604 (0.543,0.664) for new cases of JSN, COMP, IL-1β and leptin had an AUROC 0.586 (0.524,0.646) for new osteophytes, and TNF-α, IL-1β and adiponectin had an AUROC 0.590 (0.520,0.659) for new sclerosis. This large, unique study suggests different pathological processes underpinning each radiographic feature of PTOA, including predominant unbalanced ECM-catabolism and inflammation contributing to JSN, ECM-catabolism and increased inflammation contributing to osteophyte development and an inflammation-predominant process contributing to subchondral sclerosis.
{"title":"Insights into knee post-traumatic osteoarthritis pathophysiology from the relationship of serum biomarkers to radiographic features in the ADVANCE cohort","authors":"Oliver O’Sullivan, Ana M. Valdes, Fraje Watson, Stefan Kluzek, Anthony M. J. Bull, Alexander N. Bennett","doi":"10.1186/s13075-025-03648-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03648-y","url":null,"abstract":"Post-traumatic osteoarthritis (PTOA) is a complex condition with multiple pathological processes at play. Molecular biomarkers can enable a better understanding of these processes, thus enhancing case endotyping, phenotyping, personalised care and drug discovery. The longitudinal ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) study offers the opportunity to develop insights into PTOA pathophysiology using a panel of extra-cellular matrix turnover, inflammatory and metabolic biomarkers and their cross-sectional (associative) and longitudinal (predictive) relationship to features of radiographic PTOA in a cohort of young, male, severely injured servicepersonnel. Using serum and radiographic data gathered in the baseline (8-years) and first follow-up visit (11-years) post-injury of ADVANCE (n = 1145), two analyses were undertaken. Firstly, cross-sectional univariate analysis between serum COMP, CTX-II, PIIANP, IL-1b, IL-17a, TNF-a, leptin and adiponectin and radiographic features (joint space narrowing (JSN), osteophytes and sclerosis), followed by the longitudinal prediction of new or progression of these three radiographic features using LASSO to select predictors. The area under a ROC curve (AUROC) was computed. Complete radiographic and serum case data in n = 872 male British servicemen, aged 34.5 (5.5) at baseline and 38.3 (5.4) at follow-up were analysed. Those with JSN had significantly higher concentrations of leptin (FDR-corrected q-value, q = 0.04). COMP had an AUROC of 0.604 (0.543,0.664) for new cases of JSN, COMP, IL-1β and leptin had an AUROC 0.586 (0.524,0.646) for new osteophytes, and TNF-α, IL-1β and adiponectin had an AUROC 0.590 (0.520,0.659) for new sclerosis. This large, unique study suggests different pathological processes underpinning each radiographic feature of PTOA, including predominant unbalanced ECM-catabolism and inflammation contributing to JSN, ECM-catabolism and increased inflammation contributing to osteophyte development and an inflammation-predominant process contributing to subchondral sclerosis.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"78 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145441230","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}
This study investigated the clinical outcomes of stepwise dose-reduction and discontinuation protocols for biological disease-modifying anti-rheumatic drugs (bDMARD) in patients with stable rheumatoid arthritis (RA), and explored predictors of disease flares. Seventy-one patients in clinical remission for ≥ 6 months were enrolled in the Reduction group. In Phase 1, dosing intervals were extended to 1.5 and then 2.0 times the standard schedule for patients who maintained low disease activity (LDA) for ≥ 12 months. Patients who sustained LDA (n = 41) advanced to Phase 2 for complete bDMARD discontinuation. Seventy-one matched patients who continued standard therapy served as controls. In Phase 1, 12-month flare-free population rates were 80.6% in the Reduction group and 87.1% in the control group. Adverse events leading to discontinuation were rare in both groups. Gray-scale ultrasound findings were associated with flares during dose reduction (Wald χ²=2.3, p = 0.04, OR 1.06). In Phase 2, 47.5% of patients experienced flares after bDMARD discontinuation, and the 24-month flare-free population rate was significantly lower in the Reduction group (52.5%) compared to controls (86.6%) (HR 4.6, 95% CI: 2.2–11.0, p < 0.001). Serious adverse events were infrequent and occurred only in the control group. Power Doppler scores and ACPA-positivity were predictive of flares, while concomitant methotrexate use reduced flare risk. Tapering bDMARD may maintain disease control short-term, but discontinuation increases flare risk. Ultrasound findings and ACPA-positivity are valuable predictors, and concomitant methotrexate use may help prevent flares after discontinuation.
本研究调查了稳定型类风湿性关节炎（RA）患者逐步减量和停用生物疾病调节抗风湿药物（bDMARD）的临床结果，并探讨了疾病发作的预测因素。71例临床缓解≥6个月的患者被纳入减量组。在第一阶段，对于维持低疾病活动性(LDA)≥12个月的患者，给药间隔延长至标准计划的1.5倍，然后是2.0倍。持续LDA的患者（n = 41）进入2期，完全停止bDMARD。71名继续接受标准治疗的匹配患者作为对照组。在第一阶段，减少组12个月无耀斑人群率为80.6%，对照组为87.1%。导致停药的不良事件在两组中都很少见。灰度超声结果与剂量减少期间的耀斑相关（Wald χ 2 =2.3, p = 0.04, OR 1.06）。在第2期，47.5%的患者在停药后出现了急性发作，减量组24个月无急性发作的发生率（52.5%）明显低于对照组（86.6%）（HR 4.6, 95% CI: 2.2-11.0, p < 0.001）。严重不良事件很少发生，仅在对照组发生。功率多普勒评分和acpa阳性可预测耀斑，而联合使用甲氨蝶呤可降低耀斑风险。逐渐减少bDMARD可以在短期内维持疾病控制，但停用会增加爆发风险。超声检查结果和acpa阳性是有价值的预测指标，同时使用甲氨蝶呤可能有助于预防停药后的急性发作。
{"title":"Stepwise dose reduction and discontinuation of bDMARD in rheumatoid arthritis: a prospective cohort study of flare-free population, flares, and predictive markers","authors":"Yuji Nozaki, Kazuya Kishimoto, Daisuke Tomita, Tetsu Itami, Chisato Ashida, Toshihiko Shiga, Hirotaka Yamazawa, Kaori Ishimura, Yumi Morimoto, Rika Fukuda, Koji Kinoshita","doi":"10.1186/s13075-025-03672-y","DOIUrl":"https://doi.org/10.1186/s13075-025-03672-y","url":null,"abstract":"This study investigated the clinical outcomes of stepwise dose-reduction and discontinuation protocols for biological disease-modifying anti-rheumatic drugs (bDMARD) in patients with stable rheumatoid arthritis (RA), and explored predictors of disease flares. Seventy-one patients in clinical remission for ≥ 6 months were enrolled in the Reduction group. In Phase 1, dosing intervals were extended to 1.5 and then 2.0 times the standard schedule for patients who maintained low disease activity (LDA) for ≥ 12 months. Patients who sustained LDA (n = 41) advanced to Phase 2 for complete bDMARD discontinuation. Seventy-one matched patients who continued standard therapy served as controls. In Phase 1, 12-month flare-free population rates were 80.6% in the Reduction group and 87.1% in the control group. Adverse events leading to discontinuation were rare in both groups. Gray-scale ultrasound findings were associated with flares during dose reduction (Wald χ²=2.3, p = 0.04, OR 1.06). In Phase 2, 47.5% of patients experienced flares after bDMARD discontinuation, and the 24-month flare-free population rate was significantly lower in the Reduction group (52.5%) compared to controls (86.6%) (HR 4.6, 95% CI: 2.2–11.0, p < 0.001). Serious adverse events were infrequent and occurred only in the control group. Power Doppler scores and ACPA-positivity were predictive of flares, while concomitant methotrexate use reduced flare risk. Tapering bDMARD may maintain disease control short-term, but discontinuation increases flare risk. Ultrasound findings and ACPA-positivity are valuable predictors, and concomitant methotrexate use may help prevent flares after discontinuation.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"73 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435101","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}
Pub Date : 2025-11-04DOI: 10.1186/s13075-025-03666-w
Yun Kyu Kim, Jung Yoon Pyo, Ju Yeon Kim, Min Jung Kim, Su-Jin Yoo, Seo Young Park, Jin Kyun Park, Eun Young Lee, Yun Jong Lee, Seong Wook Kang, Eun Bong Lee, Jinhyun Kim, Jun Won Park
Although patients with idiopathic inflammatory myopathy (IIM) have a higher cancer risk than the general population, this risk varies among IIM patients based on clinical factors such as IIM subtype, clinical features, and autoantibody profiles. This study aimed to establish a risk-stratification system to identify those with high-risk for cancer in patients with IIM. This study included 481 patients with IIMs from four independent cohorts in South Korea. The primary outcome was myositis-associated cancer, defined as cancers occurring within 3 years before or after the diagnosis of IIM. Logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) regularization was used to select predictors from 24 prespecified factors for the multivariable model. A scoring system, entitled the SCRIM score, was established based on the β coefficient of each predictor in the final model. A conditional inference tree analysis was used to identify the optimal cut-off point for group classifications. The cancer risk of each group compared to that of the general population was assessed using standardized incidence ratio (SIR), which was calculated using the 2022 age-matched general population in South Korea as the reference. In the study population, 12.9% (n = 62) had myositis-associated cancer. The LASSO regression identified older age, male sex, current smoking status, dermatomyositis, and anti-TIF1γ as high-risk factors for cancer; however, anti-synthetase syndrome, overlap myositis, arthritis, and interstitial lung disease were associated with a lower cancer risk. The SCRIM score based on these factors showed excellent performance (AUROC 0.852 [95% CI 0.796–0.907]). Patients were stratified into the low-risk, intermediate-risk, and high-risk groups based on the SCRIM score, and the incidence of myositis-associated cancer increased significantly in a stepwise manner across groups. Patients in the low-risk group had a cancer incidence comparable to that of the general population (SIR 0.79), whereas those in the intermediate-risk (SIR 2.28) and high-risk (SIR 15.30) groups had significantly higher cancer incidences. The SCRIM score precisely stratified the risk of myositis-associated cancer for patients with IIM, which can be an important basis for establishing an evidence-based screening cancer strategy.
虽然特发性炎症性肌病（IIM）患者的癌症风险高于一般人群，但这种风险在IIM患者之间存在差异，这取决于临床因素，如IIM亚型、临床特征和自身抗体谱。本研究旨在建立一种风险分层系统来识别IIM患者的癌症高危人群。该研究包括来自韩国四个独立队列的481例IIMs患者。主要结局是肌炎相关癌症，定义为IIM诊断前后3年内发生的癌症。使用最小绝对收缩和选择算子（LASSO）正则化的逻辑回归从24个预先指定的因素中选择多变量模型的预测因子。根据最终模型中各预测因子的β系数建立评分体系，称为SCRIM评分。使用条件推理树分析来确定群体分类的最佳截断点。与普通人群相比，每组的癌症风险采用标准化发病率（SIR）进行评估，该发病率以韩国2022年年龄匹配的普通人群为参考计算得出。在研究人群中，12.9% （n = 62）患有肌炎相关癌症。LASSO回归发现年龄较大、男性、当前吸烟状况、皮肌炎和抗tif1γ是癌症的高危因素；然而，抗合成酶综合征、重叠肌炎、关节炎和间质性肺疾病与较低的癌症风险相关。基于这些因素的SCRIM评分表现优异（AUROC为0.852 [95% CI 0.796-0.907]）。根据SCRIM评分将患者分为低危、中危和高危组，肌炎相关癌症的发生率在各组间呈逐步上升趋势。低危组患者的癌症发病率与普通人群相当（SIR 0.79），而中危组（SIR 2.28）和高危组（SIR 15.30）患者的癌症发病率明显更高。SCRIM评分对IIM患者发生肌炎相关癌症的风险进行精确分层，可作为建立循证筛查癌症策略的重要依据。
{"title":"The SCRIM score: a clinical tool for cancer risk-stratification in patients with idiopathic inflammatory myopathy","authors":"Yun Kyu Kim, Jung Yoon Pyo, Ju Yeon Kim, Min Jung Kim, Su-Jin Yoo, Seo Young Park, Jin Kyun Park, Eun Young Lee, Yun Jong Lee, Seong Wook Kang, Eun Bong Lee, Jinhyun Kim, Jun Won Park","doi":"10.1186/s13075-025-03666-w","DOIUrl":"https://doi.org/10.1186/s13075-025-03666-w","url":null,"abstract":"Although patients with idiopathic inflammatory myopathy (IIM) have a higher cancer risk than the general population, this risk varies among IIM patients based on clinical factors such as IIM subtype, clinical features, and autoantibody profiles. This study aimed to establish a risk-stratification system to identify those with high-risk for cancer in patients with IIM. This study included 481 patients with IIMs from four independent cohorts in South Korea. The primary outcome was myositis-associated cancer, defined as cancers occurring within 3 years before or after the diagnosis of IIM. Logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) regularization was used to select predictors from 24 prespecified factors for the multivariable model. A scoring system, entitled the SCRIM score, was established based on the β coefficient of each predictor in the final model. A conditional inference tree analysis was used to identify the optimal cut-off point for group classifications. The cancer risk of each group compared to that of the general population was assessed using standardized incidence ratio (SIR), which was calculated using the 2022 age-matched general population in South Korea as the reference. In the study population, 12.9% (n = 62) had myositis-associated cancer. The LASSO regression identified older age, male sex, current smoking status, dermatomyositis, and anti-TIF1γ as high-risk factors for cancer; however, anti-synthetase syndrome, overlap myositis, arthritis, and interstitial lung disease were associated with a lower cancer risk. The SCRIM score based on these factors showed excellent performance (AUROC 0.852 [95% CI 0.796–0.907]). Patients were stratified into the low-risk, intermediate-risk, and high-risk groups based on the SCRIM score, and the incidence of myositis-associated cancer increased significantly in a stepwise manner across groups. Patients in the low-risk group had a cancer incidence comparable to that of the general population (SIR 0.79), whereas those in the intermediate-risk (SIR 2.28) and high-risk (SIR 15.30) groups had significantly higher cancer incidences. The SCRIM score precisely stratified the risk of myositis-associated cancer for patients with IIM, which can be an important basis for establishing an evidence-based screening cancer strategy.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"28 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435020","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}
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