Matteo Becatti, Giacomo Emmi, Alessandra Bettiol, Amanda Mannucci, Flavia Rita Argento, Eleonora Fini, Serena Borghi, Francesca Nencini, Maria Nicastro, Irene Mattioli, Elena Silvestri, Augusto Vaglio, Domenico Prisco, Claudia Fiorillo
{"title":"ROS诱导的纤维蛋白凝块修饰将系统性红斑狼疮患者的免疫反应与动脉粥样硬化血栓形成联系起来","authors":"Matteo Becatti, Giacomo Emmi, Alessandra Bettiol, Amanda Mannucci, Flavia Rita Argento, Eleonora Fini, Serena Borghi, Francesca Nencini, Maria Nicastro, Irene Mattioli, Elena Silvestri, Augusto Vaglio, Domenico Prisco, Claudia Fiorillo","doi":"10.1002/art.43371","DOIUrl":null,"url":null,"abstract":"ObjectiveCardiovascular events are major determinants of morbidity and mortality in systemic lupus erythematosus (SLE), particularly in patients with renal involvement. While oxidative stress has been implicated in driving vascular and renal damage in SLE, the specific mechanisms remain unclear. This study investigated the potential role of oxidative stress‐induced alterations in fibrinogen structure and function in the pathogenesis of atherothrombosis in SLE.MethodsIn this cross‐sectional study, we enrolled 144 adult patients with SLE and 90 matched controls. We measured blood leukocyte reactive oxygen species (ROS) production, systemic redox status, and the structural and functional features of purified fibrinogen. Correlations between these parameters and disease activity were also investigated. <jats:italic>In vitro</jats:italic> experiments to clarify the causal relationships among ROS levels, protein oxidation, and fibrin abnormalities provided mechanistic insights of the observed alterations.ResultsSLE patients showed increased leukocyte ROS production, mainly due to neutrophil NADPH oxidase activation. Interestingly, renal biopsies from SLE patients with active proliferative lupus nephritis exhibited the NADPH oxidase enzyme complex p22phox overexpression. This was accompanied by plasma oxidative stress as indicated by elevated plasma lipid peroxidation and reduced antioxidant defenses. Fibrinogen oxidation was associated with structural and functional changes, leading to the formation of denser fibrin networks with lower clot porosity and reduced susceptibility to plasmin‐mediated fibrin lysis. Interestingly, these fibrinogen modifications correlated with alterations in redox status and disease activity.ConclusionOxidative stress may drive structural and functional modifications of fibrinogen in SLE, potentially acting as a novel pathogenetic mechanism in atherothrombosis among these patients.","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":10.9000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ROS‐induced modifications of fibrin clots connect immune responses to atherothrombosis in systemic lupus erythematosus\",\"authors\":\"Matteo Becatti, Giacomo Emmi, Alessandra Bettiol, Amanda Mannucci, Flavia Rita Argento, Eleonora Fini, Serena Borghi, Francesca Nencini, Maria Nicastro, Irene Mattioli, Elena Silvestri, Augusto Vaglio, Domenico Prisco, Claudia Fiorillo\",\"doi\":\"10.1002/art.43371\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"ObjectiveCardiovascular events are major determinants of morbidity and mortality in systemic lupus erythematosus (SLE), particularly in patients with renal involvement. While oxidative stress has been implicated in driving vascular and renal damage in SLE, the specific mechanisms remain unclear. This study investigated the potential role of oxidative stress‐induced alterations in fibrinogen structure and function in the pathogenesis of atherothrombosis in SLE.MethodsIn this cross‐sectional study, we enrolled 144 adult patients with SLE and 90 matched controls. We measured blood leukocyte reactive oxygen species (ROS) production, systemic redox status, and the structural and functional features of purified fibrinogen. Correlations between these parameters and disease activity were also investigated. <jats:italic>In vitro</jats:italic> experiments to clarify the causal relationships among ROS levels, protein oxidation, and fibrin abnormalities provided mechanistic insights of the observed alterations.ResultsSLE patients showed increased leukocyte ROS production, mainly due to neutrophil NADPH oxidase activation. Interestingly, renal biopsies from SLE patients with active proliferative lupus nephritis exhibited the NADPH oxidase enzyme complex p22phox overexpression. This was accompanied by plasma oxidative stress as indicated by elevated plasma lipid peroxidation and reduced antioxidant defenses. Fibrinogen oxidation was associated with structural and functional changes, leading to the formation of denser fibrin networks with lower clot porosity and reduced susceptibility to plasmin‐mediated fibrin lysis. Interestingly, these fibrinogen modifications correlated with alterations in redox status and disease activity.ConclusionOxidative stress may drive structural and functional modifications of fibrinogen in SLE, potentially acting as a novel pathogenetic mechanism in atherothrombosis among these patients.\",\"PeriodicalId\":129,\"journal\":{\"name\":\"Arthritis & Rheumatology\",\"volume\":\"24 1\",\"pages\":\"\"},\"PeriodicalIF\":10.9000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Arthritis & Rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/art.43371\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arthritis & Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/art.43371","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
ROS‐induced modifications of fibrin clots connect immune responses to atherothrombosis in systemic lupus erythematosus
ObjectiveCardiovascular events are major determinants of morbidity and mortality in systemic lupus erythematosus (SLE), particularly in patients with renal involvement. While oxidative stress has been implicated in driving vascular and renal damage in SLE, the specific mechanisms remain unclear. This study investigated the potential role of oxidative stress‐induced alterations in fibrinogen structure and function in the pathogenesis of atherothrombosis in SLE.MethodsIn this cross‐sectional study, we enrolled 144 adult patients with SLE and 90 matched controls. We measured blood leukocyte reactive oxygen species (ROS) production, systemic redox status, and the structural and functional features of purified fibrinogen. Correlations between these parameters and disease activity were also investigated. In vitro experiments to clarify the causal relationships among ROS levels, protein oxidation, and fibrin abnormalities provided mechanistic insights of the observed alterations.ResultsSLE patients showed increased leukocyte ROS production, mainly due to neutrophil NADPH oxidase activation. Interestingly, renal biopsies from SLE patients with active proliferative lupus nephritis exhibited the NADPH oxidase enzyme complex p22phox overexpression. This was accompanied by plasma oxidative stress as indicated by elevated plasma lipid peroxidation and reduced antioxidant defenses. Fibrinogen oxidation was associated with structural and functional changes, leading to the formation of denser fibrin networks with lower clot porosity and reduced susceptibility to plasmin‐mediated fibrin lysis. Interestingly, these fibrinogen modifications correlated with alterations in redox status and disease activity.ConclusionOxidative stress may drive structural and functional modifications of fibrinogen in SLE, potentially acting as a novel pathogenetic mechanism in atherothrombosis among these patients.
期刊介绍:
Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.