基于质谱的精准诊断技术为抗凝血酶缺乏症提供了新见解。

IF 5.5 2区 医学 Q1 HEMATOLOGY Journal of Thrombosis and Haemostasis Pub Date : 2024-10-16 DOI:10.1016/j.jtha.2024.10.005
Mirjam Kruijt, Maria Eugenia de la Morena-Barrio, Javier Corral, Christa M Cobbaert, L Renee Ruhaak
{"title":"基于质谱的精准诊断技术为抗凝血酶缺乏症提供了新见解。","authors":"Mirjam Kruijt, Maria Eugenia de la Morena-Barrio, Javier Corral, Christa M Cobbaert, L Renee Ruhaak","doi":"10.1016/j.jtha.2024.10.005","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Although P5 (preventive, personalized, predictive, participatory, psychocognitive) medicine and patient focused healthcare are gaining ground in various healthcare areas, the diagnosis of antithrombin deficiency (ATD) is still based on crude diagnostic tests clustering patients into clinically heterogeneous subgroups whereby relevant thrombophilia phenotypes may go unnoticed. Clinical pathways and the majority of evidence are based on these tests, therefore generic treatment is still the norm.</p><p><strong>Objectives: </strong>To unravel the heterogeneity of ATD, a mass spectrometry (LC-MRM-MS)-based test for antithrombin was developed allowing molecular characterization of the antithrombin proteoforms in patient plasma. This study provides the first insight into the tests' clinical performance.</p><p><strong>Methods: </strong>Plasma from 91 unrelated ATD patients and 41 patients with a congenital disorder of glycosylation affecting antithrombin glycosylation were characterized functionally, genetically, and analyzed by LC-MRM-MS. An established data analysis strategy was applied for quantitation and molecular characterization of antithrombin proteoforms.</p><p><strong>Results: </strong>The test recognized patients with a quantitative defect, discriminated between type I and type II ATD, and identified variant proteoforms. Overall, the diagnostic sensitivity for ATD was 100% for LC-MRM-MS compared to 81.1% by the functional test. Type II ATD, a subtype prone to misdiagnosis, revealed an even larger difference of 100% identification by LC-MRM-MS versus 56.8% by functional test.</p><p><strong>Conclusions: </strong>The qualitative and quantitative MS-based AT-test can serve as a platform for investigating the molecular basis of the clinical heterogeneity of ATD. This Precision Diagnostics approach for ATD can lower diagnostic uncertainty and modernize the ATD diagnostic and clinical pathways.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel insights into Antithrombin Deficiency enabled by Mass Spectrometry-based Precision Diagnostics.\",\"authors\":\"Mirjam Kruijt, Maria Eugenia de la Morena-Barrio, Javier Corral, Christa M Cobbaert, L Renee Ruhaak\",\"doi\":\"10.1016/j.jtha.2024.10.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Although P5 (preventive, personalized, predictive, participatory, psychocognitive) medicine and patient focused healthcare are gaining ground in various healthcare areas, the diagnosis of antithrombin deficiency (ATD) is still based on crude diagnostic tests clustering patients into clinically heterogeneous subgroups whereby relevant thrombophilia phenotypes may go unnoticed. Clinical pathways and the majority of evidence are based on these tests, therefore generic treatment is still the norm.</p><p><strong>Objectives: </strong>To unravel the heterogeneity of ATD, a mass spectrometry (LC-MRM-MS)-based test for antithrombin was developed allowing molecular characterization of the antithrombin proteoforms in patient plasma. This study provides the first insight into the tests' clinical performance.</p><p><strong>Methods: </strong>Plasma from 91 unrelated ATD patients and 41 patients with a congenital disorder of glycosylation affecting antithrombin glycosylation were characterized functionally, genetically, and analyzed by LC-MRM-MS. An established data analysis strategy was applied for quantitation and molecular characterization of antithrombin proteoforms.</p><p><strong>Results: </strong>The test recognized patients with a quantitative defect, discriminated between type I and type II ATD, and identified variant proteoforms. Overall, the diagnostic sensitivity for ATD was 100% for LC-MRM-MS compared to 81.1% by the functional test. Type II ATD, a subtype prone to misdiagnosis, revealed an even larger difference of 100% identification by LC-MRM-MS versus 56.8% by functional test.</p><p><strong>Conclusions: </strong>The qualitative and quantitative MS-based AT-test can serve as a platform for investigating the molecular basis of the clinical heterogeneity of ATD. This Precision Diagnostics approach for ATD can lower diagnostic uncertainty and modernize the ATD diagnostic and clinical pathways.</p>\",\"PeriodicalId\":17326,\"journal\":{\"name\":\"Journal of Thrombosis and Haemostasis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Thrombosis and Haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jtha.2024.10.005\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtha.2024.10.005","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:尽管五常法(预防性、个性化、预测性、参与性、心理认知)医学和以患者为中心的医疗保健在各个医疗保健领域日益普及,但抗凝血酶缺乏症(ATD)的诊断仍以粗略的诊断测试为基础,将患者分为临床异质性亚组,相关的血栓性表型可能因此而被忽视。临床路径和大多数证据都以这些测试为基础,因此普通治疗仍是常态:为了揭示 ATD 的异质性,我们开发了一种基于质谱(LC-MRM-MS)的抗凝血酶检测方法,可对患者血浆中的抗凝血酶蛋白形式进行分子鉴定。本研究首次揭示了该检测方法的临床性能:方法:91 名无血缘关系的 ATD 患者和 41 名患有影响抗凝血酶糖基化的先天性糖基化紊乱的患者的血浆进行了功能和基因表征,并通过 LC-MRM-MS 进行了分析。采用既定的数据分析策略对抗凝血酶蛋白形式进行定量和分子鉴定:结果:该检测能识别存在定量缺陷的患者,区分 I 型和 II 型 ATD,并识别出变异蛋白形式。总体而言,LC-MRM-MS 对 ATD 的诊断灵敏度为 100%,而功能测试的灵敏度为 81.1%。II 型 ATD 是一种容易误诊的亚型,LC-MRM-MS 与功能测试的识别率差异更大,前者为 100%,后者为 56.8%:基于 MS 的定性和定量 AT 测试可作为研究 ATD 临床异质性分子基础的平台。这种针对 ATD 的精准诊断方法可以降低诊断的不确定性,并使 ATD 诊断和临床路径现代化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Novel insights into Antithrombin Deficiency enabled by Mass Spectrometry-based Precision Diagnostics.

Background: Although P5 (preventive, personalized, predictive, participatory, psychocognitive) medicine and patient focused healthcare are gaining ground in various healthcare areas, the diagnosis of antithrombin deficiency (ATD) is still based on crude diagnostic tests clustering patients into clinically heterogeneous subgroups whereby relevant thrombophilia phenotypes may go unnoticed. Clinical pathways and the majority of evidence are based on these tests, therefore generic treatment is still the norm.

Objectives: To unravel the heterogeneity of ATD, a mass spectrometry (LC-MRM-MS)-based test for antithrombin was developed allowing molecular characterization of the antithrombin proteoforms in patient plasma. This study provides the first insight into the tests' clinical performance.

Methods: Plasma from 91 unrelated ATD patients and 41 patients with a congenital disorder of glycosylation affecting antithrombin glycosylation were characterized functionally, genetically, and analyzed by LC-MRM-MS. An established data analysis strategy was applied for quantitation and molecular characterization of antithrombin proteoforms.

Results: The test recognized patients with a quantitative defect, discriminated between type I and type II ATD, and identified variant proteoforms. Overall, the diagnostic sensitivity for ATD was 100% for LC-MRM-MS compared to 81.1% by the functional test. Type II ATD, a subtype prone to misdiagnosis, revealed an even larger difference of 100% identification by LC-MRM-MS versus 56.8% by functional test.

Conclusions: The qualitative and quantitative MS-based AT-test can serve as a platform for investigating the molecular basis of the clinical heterogeneity of ATD. This Precision Diagnostics approach for ATD can lower diagnostic uncertainty and modernize the ATD diagnostic and clinical pathways.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis 医学-外周血管病
CiteScore
24.30
自引率
3.80%
发文量
321
审稿时长
1 months
期刊介绍: The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
期刊最新文献
An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: Guidance from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee (ISTH-SSC) Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. The severe von Willebrand Disease variant p.M771V leads to impaired anterograde trafficking of Von Willebrand factor in patient-derived and base-edited ECFCs. Validating International Classification of Diseases Code 10th Revision algorithms for accurate identification of pulmonary embolism. High risk of long-term recurrence after a first episode of venous thromboembolism during pregnancy or postpartum: the REcurrence after a PrEgnAncy related Thrombosis (REPEAT) Study. Validation of clinical risk assessment scores for venous thromboembolism in patients with cancer: a population-based cohort study.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1