Adrianna Klajmon, Joanna Natorska, Javier Corral, Maria Eugenia de la Morena-Barrio, Carlos Bravo-Pérez, Magdalena Kopytek, Urszula Jankowska, Bozena Skupien-Rabian, Maksymilian Hanarz, Jacek Treliński, Michał Ząbczyk
{"title":"血浆硒蛋白 P 的减少与 I 型抗凝血酶缺乏症和血栓形成前状态有关。","authors":"Adrianna Klajmon, Joanna Natorska, Javier Corral, Maria Eugenia de la Morena-Barrio, Carlos Bravo-Pérez, Magdalena Kopytek, Urszula Jankowska, Bozena Skupien-Rabian, Maksymilian Hanarz, Jacek Treliński, Michał Ząbczyk","doi":"10.5858/arpa.2024-0162-OA","DOIUrl":null,"url":null,"abstract":"<p><strong>Context.—: </strong>A positive association between antithrombin activity and selenium level was reported. Selenoprotein P, the most important selenium carrier, was identified within human plasma fibrin clots.</p><p><strong>Objective.—: </strong>To investigate the relationship between selenoprotein P and antithrombin and its role in modulation of fibrin clot properties in antithrombin-deficient patients.</p><p><strong>Design.—: </strong>Proteomic analysis of plasma fibrin clots was performed with mass spectrometry. In 108 patients with genetically confirmed type I (57%) or type II (43%) antithrombin deficiency and in healthy controls (n = 50), we assessed plasma selenoprotein P levels and thiobarbituric acid-reactive substances by enzyme-linked immunosorbent assay, along with fibrin clot permeability, clot lysis time, and thrombin generation.</p><p><strong>Results.—: </strong>Clot-bound antithrombin concentration was 0.46 ± 0.32 mg/g protein, while selenoprotein P level was 30-fold lower (0.015 ± 0.012 mg/g). Type I compared to type II antithrombin-deficient patients had higher clot-bound antithrombin and selenoprotein P levels (both P < .001), associated together (ρ = 0.93, P < .001). Individuals with type I compared to type II antithrombin deficiency or controls had about 40% lower plasma selenoprotein P levels (P < .001). In antithrombin-deficient patients, plasma selenoprotein P was associated with antithrombin antigen (ρ = 0.35, P < .001) and thiobarbituric acid-reactive substances (ρ = 0.42, P < .001). Plasma selenoprotein P correlated also with endogenous thrombin potential (r = -0.33, P < .001), fibrin clot permeability (r = 0.43, P < .001), and clot lysis time (r = -0.40, P < .001) in antithrombin-deficient patients but not in controls.</p><p><strong>Conclusions.—: </strong>Patients with type I antithrombin deficiency had higher clot-bound selenoprotein P and reduced plasma selenoprotein P levels. Plasma selenoprotein P was associated with prothrombotic fibrin clot phenotype and enhanced thrombin generation.</p>","PeriodicalId":93883,"journal":{"name":"Archives of pathology & laboratory medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Reduced Plasma Selenoprotein P Is Associated With Type I Antithrombin Deficiency and a Prothrombotic State.\",\"authors\":\"Adrianna Klajmon, Joanna Natorska, Javier Corral, Maria Eugenia de la Morena-Barrio, Carlos Bravo-Pérez, Magdalena Kopytek, Urszula Jankowska, Bozena Skupien-Rabian, Maksymilian Hanarz, Jacek Treliński, Michał Ząbczyk\",\"doi\":\"10.5858/arpa.2024-0162-OA\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context.—: </strong>A positive association between antithrombin activity and selenium level was reported. Selenoprotein P, the most important selenium carrier, was identified within human plasma fibrin clots.</p><p><strong>Objective.—: </strong>To investigate the relationship between selenoprotein P and antithrombin and its role in modulation of fibrin clot properties in antithrombin-deficient patients.</p><p><strong>Design.—: </strong>Proteomic analysis of plasma fibrin clots was performed with mass spectrometry. In 108 patients with genetically confirmed type I (57%) or type II (43%) antithrombin deficiency and in healthy controls (n = 50), we assessed plasma selenoprotein P levels and thiobarbituric acid-reactive substances by enzyme-linked immunosorbent assay, along with fibrin clot permeability, clot lysis time, and thrombin generation.</p><p><strong>Results.—: </strong>Clot-bound antithrombin concentration was 0.46 ± 0.32 mg/g protein, while selenoprotein P level was 30-fold lower (0.015 ± 0.012 mg/g). Type I compared to type II antithrombin-deficient patients had higher clot-bound antithrombin and selenoprotein P levels (both P < .001), associated together (ρ = 0.93, P < .001). Individuals with type I compared to type II antithrombin deficiency or controls had about 40% lower plasma selenoprotein P levels (P < .001). In antithrombin-deficient patients, plasma selenoprotein P was associated with antithrombin antigen (ρ = 0.35, P < .001) and thiobarbituric acid-reactive substances (ρ = 0.42, P < .001). Plasma selenoprotein P correlated also with endogenous thrombin potential (r = -0.33, P < .001), fibrin clot permeability (r = 0.43, P < .001), and clot lysis time (r = -0.40, P < .001) in antithrombin-deficient patients but not in controls.</p><p><strong>Conclusions.—: </strong>Patients with type I antithrombin deficiency had higher clot-bound selenoprotein P and reduced plasma selenoprotein P levels. Plasma selenoprotein P was associated with prothrombotic fibrin clot phenotype and enhanced thrombin generation.</p>\",\"PeriodicalId\":93883,\"journal\":{\"name\":\"Archives of pathology & laboratory medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of pathology & laboratory medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5858/arpa.2024-0162-OA\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of pathology & laboratory medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5858/arpa.2024-0162-OA","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景据报道，抗凝血酶活性与硒水平呈正相关。硒蛋白 P 是人体血浆纤维蛋白凝块中最重要的硒载体：研究硒蛋白 P 与抗凝血酶之间的关系及其在调节抗凝血酶缺乏症患者纤维蛋白凝块特性中的作用：采用质谱法对血浆纤维蛋白凝块进行蛋白质组分析。在 108 名经基因证实的 I 型（57%）或 II 型（43%）抗凝血酶缺乏症患者和健康对照组（n = 50）中，我们通过酶联免疫吸附测定法评估了血浆硒蛋白 P 水平和硫代巴比妥酸反应物质，以及纤维蛋白凝块渗透性、凝块溶解时间和凝血酶生成情况：凝块结合抗凝血酶浓度为 0.46 ± 0.32 毫克/克蛋白质，而硒蛋白 P 水平则低 30 倍（0.015 ± 0.012 毫克/克）。与 II 型抗凝血酶缺乏症患者相比，I 型患者的凝血结合抗凝血酶和硒蛋白 P 水平更高（均为 P < .001），两者相关联（ρ = 0.93，P < .001）。与 II 型抗凝血酶缺乏症或对照组相比，I 型抗凝血酶缺乏症患者的血浆硒蛋白 P 水平要低 40% 左右（P < .001）。在抗凝血酶缺乏症患者中，血浆硒蛋白 P 与抗凝血酶抗原（ρ = 0.35，P < .001）和硫代巴比妥酸反应物质（ρ = 0.42，P < .001）相关。在抗凝血酶缺乏症患者中，血浆硒蛋白 P 还与内源性凝血酶潜能（r = -0.33，P < .001）、纤维蛋白凝块渗透性（r = 0.43，P < .001）和凝块溶解时间（r = -0.40，P < .001）相关，而在对照组中则不相关：结论：I型抗凝血酶缺乏症患者血凝块结合的硒蛋白P较高，血浆硒蛋白P水平较低。血浆硒蛋白 P 与促血栓形成的纤维蛋白凝块表型和凝血酶生成增强有关。
Reduced Plasma Selenoprotein P Is Associated With Type I Antithrombin Deficiency and a Prothrombotic State.
Context.—: A positive association between antithrombin activity and selenium level was reported. Selenoprotein P, the most important selenium carrier, was identified within human plasma fibrin clots.
Objective.—: To investigate the relationship between selenoprotein P and antithrombin and its role in modulation of fibrin clot properties in antithrombin-deficient patients.
Design.—: Proteomic analysis of plasma fibrin clots was performed with mass spectrometry. In 108 patients with genetically confirmed type I (57%) or type II (43%) antithrombin deficiency and in healthy controls (n = 50), we assessed plasma selenoprotein P levels and thiobarbituric acid-reactive substances by enzyme-linked immunosorbent assay, along with fibrin clot permeability, clot lysis time, and thrombin generation.
Results.—: Clot-bound antithrombin concentration was 0.46 ± 0.32 mg/g protein, while selenoprotein P level was 30-fold lower (0.015 ± 0.012 mg/g). Type I compared to type II antithrombin-deficient patients had higher clot-bound antithrombin and selenoprotein P levels (both P < .001), associated together (ρ = 0.93, P < .001). Individuals with type I compared to type II antithrombin deficiency or controls had about 40% lower plasma selenoprotein P levels (P < .001). In antithrombin-deficient patients, plasma selenoprotein P was associated with antithrombin antigen (ρ = 0.35, P < .001) and thiobarbituric acid-reactive substances (ρ = 0.42, P < .001). Plasma selenoprotein P correlated also with endogenous thrombin potential (r = -0.33, P < .001), fibrin clot permeability (r = 0.43, P < .001), and clot lysis time (r = -0.40, P < .001) in antithrombin-deficient patients but not in controls.
Conclusions.—: Patients with type I antithrombin deficiency had higher clot-bound selenoprotein P and reduced plasma selenoprotein P levels. Plasma selenoprotein P was associated with prothrombotic fibrin clot phenotype and enhanced thrombin generation.
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