Matthew Nichols , Chai W. Phua , Martha L. Louzada , Benjamin D. Hedley , Vipin Bhayana , Ian Chin-Yee , Angela C. Rutledge
{"title":"使用安捷伦AssayMAP Bravo液体处理系统耦合LC-QTOF增强多发性骨髓瘤患者m蛋白的检测和表征","authors":"Matthew Nichols , Chai W. Phua , Martha L. Louzada , Benjamin D. Hedley , Vipin Bhayana , Ian Chin-Yee , Angela C. Rutledge","doi":"10.1016/j.clinbiochem.2024.110870","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Mass spectrometry methods are emerging as tools to detect M−proteins in the serum of multiple myeloma patients with increased sensitivity and specificity compared to traditional electrophoretic methods.</div></div><div><h3>Methods</h3><div>A liquid handling system, the Agilent AssayMAP Bravo, with liquid chromatography high-resolution quadrupole-time-of-flight (LC-QTOF) mass spectrometry to analyze intact light chains was compared to immunofixation electrophoresis (IFE) for M−protein analysis. 210 patient serum samples were analyzed in a split sample comparison (LC-QTOF vs. IFE). LC-QTOF and IFE were interpreted by different individuals in a blinded fashion and results were grouped into four categories: IFE+/QTOF+, IFE+/QTOF-, IFE-/QTOF+, or IFE-/QTOF-.</div></div><div><h3>Results</h3><div>The LC-QTOF method is able to determine the isotype of M−proteins in a similar fashion to IFE. The estimated limit of detection was ∼ 35 mg/L for adalimumab. For split patient samples, 168 were QTOF+/IFE+, 25 were QTOF-/IFE-, 14 were QTOF+/IFE-, and three were QTOF-/IFE + . Excluding the QTOF+/IFE- results due to the improved sensitivity of the LC-QTOF method, the concordance of LC-QTOF with IFE was ∼ 98 %. The LC-QTOF method also offers improved specificity compared to electrophoretic methods due to inclusion of the accurate mass of the light chains.</div></div><div><h3>Conclusions</h3><div>The LC-QTOF method was deemed fit for clinical use as a qualitative test with increased sensitivity and specificity compared to IFE. The LC-QTOF can also better resolve therapeutic and multiple myeloma IgG-kappa M−proteins, which present a challenge for electrophoretic methods. Future work will determine suitability of this method as an assessment of minimal residual disease status.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110870"},"PeriodicalIF":2.5000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhanced detection and Characterization of M-proteins in multiple myeloma patients using An Agilent AssayMAP Bravo liquid handling system coupled to an LC-QTOF\",\"authors\":\"Matthew Nichols , Chai W. Phua , Martha L. Louzada , Benjamin D. Hedley , Vipin Bhayana , Ian Chin-Yee , Angela C. Rutledge\",\"doi\":\"10.1016/j.clinbiochem.2024.110870\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Mass spectrometry methods are emerging as tools to detect M−proteins in the serum of multiple myeloma patients with increased sensitivity and specificity compared to traditional electrophoretic methods.</div></div><div><h3>Methods</h3><div>A liquid handling system, the Agilent AssayMAP Bravo, with liquid chromatography high-resolution quadrupole-time-of-flight (LC-QTOF) mass spectrometry to analyze intact light chains was compared to immunofixation electrophoresis (IFE) for M−protein analysis. 210 patient serum samples were analyzed in a split sample comparison (LC-QTOF vs. IFE). LC-QTOF and IFE were interpreted by different individuals in a blinded fashion and results were grouped into four categories: IFE+/QTOF+, IFE+/QTOF-, IFE-/QTOF+, or IFE-/QTOF-.</div></div><div><h3>Results</h3><div>The LC-QTOF method is able to determine the isotype of M−proteins in a similar fashion to IFE. The estimated limit of detection was ∼ 35 mg/L for adalimumab. For split patient samples, 168 were QTOF+/IFE+, 25 were QTOF-/IFE-, 14 were QTOF+/IFE-, and three were QTOF-/IFE + . Excluding the QTOF+/IFE- results due to the improved sensitivity of the LC-QTOF method, the concordance of LC-QTOF with IFE was ∼ 98 %. The LC-QTOF method also offers improved specificity compared to electrophoretic methods due to inclusion of the accurate mass of the light chains.</div></div><div><h3>Conclusions</h3><div>The LC-QTOF method was deemed fit for clinical use as a qualitative test with increased sensitivity and specificity compared to IFE. The LC-QTOF can also better resolve therapeutic and multiple myeloma IgG-kappa M−proteins, which present a challenge for electrophoretic methods. Future work will determine suitability of this method as an assessment of minimal residual disease status.</div></div>\",\"PeriodicalId\":10172,\"journal\":{\"name\":\"Clinical biochemistry\",\"volume\":\"135 \",\"pages\":\"Article 110870\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical biochemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0009912024001644\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical biochemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0009912024001644","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Enhanced detection and Characterization of M-proteins in multiple myeloma patients using An Agilent AssayMAP Bravo liquid handling system coupled to an LC-QTOF
Background
Mass spectrometry methods are emerging as tools to detect M−proteins in the serum of multiple myeloma patients with increased sensitivity and specificity compared to traditional electrophoretic methods.
Methods
A liquid handling system, the Agilent AssayMAP Bravo, with liquid chromatography high-resolution quadrupole-time-of-flight (LC-QTOF) mass spectrometry to analyze intact light chains was compared to immunofixation electrophoresis (IFE) for M−protein analysis. 210 patient serum samples were analyzed in a split sample comparison (LC-QTOF vs. IFE). LC-QTOF and IFE were interpreted by different individuals in a blinded fashion and results were grouped into four categories: IFE+/QTOF+, IFE+/QTOF-, IFE-/QTOF+, or IFE-/QTOF-.
Results
The LC-QTOF method is able to determine the isotype of M−proteins in a similar fashion to IFE. The estimated limit of detection was ∼ 35 mg/L for adalimumab. For split patient samples, 168 were QTOF+/IFE+, 25 were QTOF-/IFE-, 14 were QTOF+/IFE-, and three were QTOF-/IFE + . Excluding the QTOF+/IFE- results due to the improved sensitivity of the LC-QTOF method, the concordance of LC-QTOF with IFE was ∼ 98 %. The LC-QTOF method also offers improved specificity compared to electrophoretic methods due to inclusion of the accurate mass of the light chains.
Conclusions
The LC-QTOF method was deemed fit for clinical use as a qualitative test with increased sensitivity and specificity compared to IFE. The LC-QTOF can also better resolve therapeutic and multiple myeloma IgG-kappa M−proteins, which present a challenge for electrophoretic methods. Future work will determine suitability of this method as an assessment of minimal residual disease status.
期刊介绍:
Clinical Biochemistry publishes articles relating to clinical chemistry, molecular biology and genetics, therapeutic drug monitoring and toxicology, laboratory immunology and laboratory medicine in general, with the focus on analytical and clinical investigation of laboratory tests in humans used for diagnosis, prognosis, treatment and therapy, and monitoring of disease.