Augmented thrombin formation is related to circulating levels of extracellular vesicles exposing tissue factor and citrullinated histone-3 in anti-neutrophil cytoplasmic antibody-associated vasculitides

Frontiers in Medicine

Medicine

Annette Bruchfeld¹  Asta Dogg Jonasdottir²  Fariborz Mobarrez³  Annica Nordin⁴  Aleksandra Antovic⁵  Iva Gunnarsson⁵  Milena Manojlovic⁶  Jelena Vojinovic⁶ 

[1] Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden;Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden;Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet, Stockholm, Sweden;Division of Nephrology, Department of Medicine, Landspitali – The National University Hospital, Reykjavik, Iceland;Department of Medical Sciences, Uppsala University, Uppsala, Sweden;Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden;Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden;Rheumatology, Karolinska University Hospital Stockholm, Stockholm, Sweden;Department of Pediatrics, Medical Faculty, University of Niš, Niš, Serbia;

关键词: anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis;    extracellular vesicles;    thrombin generation;    NETs;    tissue factor;   

DOI  :  10.3389/fmed.2023.1240325

 received in 2023-06-14, accepted in 2023-09-29,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectivesTo study circulating myeloperoxidase (MPO)-positive extracellular vesicles (MPO+EVs) exposing citrullinated histone-3 (H3Cit), tissue factor (TF), and plasminogen (Plg) in association to thrombin generation in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).MethodsWe have involved well-characterized patients with AAV together with population-based controls. Flow cytometry was used to assess the levels of MPO+EVs in citrated plasma. MPO+EVs were phenotyped by anti-MPO-antibodies together with anti-CD142 (anti-TF), anti-H3Cit, and anti-Plg antibodies. A modified Calibrated Automated Thrombogram (CAT) assay was utilized to measure thrombin generation in plasma initiated by EVs-enriched pellets. The activity of AAV was evaluated with the Birmingham Vasculitis Activity Score (BVAS).ResultsThis study comprised 46 AAV patients, 23 in the active stage of the disease and 23 in remission, as well as 23 age- and sex matched population-based controls. Augmented levels of all investigated MPO+ EVs were found in active AAV patients in comparison to the subgroup of patients in remission and controls. Thrombin generation, measured by endogenous thrombin potential (ETP) and peak of thrombin formation, was higher in plasma when triggered by EVs-enriched pellet from AAV patients. ETP and peak were associated with the levels of MPO+TF+ and MPO+H3Cit+ EVs. Additionally, MPO+TF+ EVs correlated with the disease activity evaluated with BVAS.ConclusionAugmented thrombin generation is found in AAV patients regardless of disease activity and is associated with higher exposure of TF and H3Cit on MPO+EVs. This may contribute to the increased risk of thrombosis seen in AAV patients.

【 授权许可】

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Copyright © 2023 Jonasdottir, Manojlovic, Vojinovic, Nordin, Bruchfeld, Gunnarsson, Mobarrez and Antovic.