Enhanced detection and Characterization of M-proteins in multiple myeloma patients using An Agilent AssayMAP Bravo liquid handling system coupled to an LC-QTOF

IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Clinical biochemistry Pub Date : 2025-01-01 DOI:10.1016/j.clinbiochem.2024.110870
Matthew Nichols , Chai W. Phua , Martha L. Louzada , Benjamin D. Hedley , Vipin Bhayana , Ian Chin-Yee , Angela C. Rutledge
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Abstract

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.
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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
背景:质谱法正在成为检测多发性骨髓瘤患者血清中m蛋白的工具,与传统的电泳方法相比,其灵敏度和特异性都有所提高。方法:采用液体处理系统Agilent AssayMAP Bravo,采用液相色谱高分辨率四极杆飞行时间(LC-QTOF)质谱法分析完整轻链,与免疫固定电泳(IFE)分析m蛋白进行比较。210例患者血清样本进行了拆分样本比较(LC-QTOF vs. IFE)。LC-QTOF和IFE由不同的个体以盲法解释,结果分为四类:IFE+/QTOF+、IFE+/QTOF-、IFE-/QTOF+或IFE-/QTOF-。结果:LC-QTOF方法能够以与IFE相似的方式确定m蛋白的同型。阿达木单抗的估计检出限为 ~ 35 mg/L。对于拆分的患者样本,168例QTOF+/IFE+, 25例QTOF-/IFE-, 14例QTOF+/IFE-, 3例QTOF-/IFE + 。排除由于LC-QTOF方法灵敏度提高而导致的QTOF+/IFE-结果,LC-QTOF与IFE的一致性为 ~ 98 %。由于LC-QTOF方法包含了轻链的精确质量,因此与电泳方法相比,LC-QTOF方法还提供了更好的特异性。结论:LC-QTOF作为一种定性检测方法,与IFE相比具有更高的灵敏度和特异性,适合临床应用。LC-QTOF还可以更好地分辨治疗性和多发性骨髓瘤IgG-kappa m蛋白,这对电泳方法提出了挑战。未来的工作将确定该方法作为最小残留疾病状态评估的适用性。
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来源期刊
Clinical biochemistry
Clinical biochemistry 医学-医学实验技术
CiteScore
5.10
自引率
0.00%
发文量
151
审稿时长
25 days
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.
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