Background Immunoglobulin (Ig) measurements in the clinical laboratory have been traditionally performed by nephelometry, turbidimetry, electrophoresis, and ELISA assays. Mass spectrometry (MS) measurements have the potential to provide deeper insights on the nature of these markers. Content Different approaches—top-down, middle-down, or bottom-up—have been described for measuring specific Igs for endogenous monoclonal immunoglobulins (M-proteins) and exogenous therapeutic monoclonal antibody therapies (t-mAbs). Challenges arise in distinguishing the Ig of interest from the polyclonal Ig background. MS is emerging as a practical method to provide quantitative analysis and information about structural and clonal features that are not easily determined by current clinical laboratory methods. This review discusses clinically implemented examples, including isotyping and quantification of M-proteins and quantitation of t-mAbs within the polyclonal Ig background, as examples of how MS can enhance our detection and characterization of Igs. Summary This review of current clinically available MS proteomic tests for Igs highlights both analytical and nonanalytical challenges for implementation. Given the new insight into Igs from these methods, it is hoped that vendors, laboratorians, healthcare providers, and payment systems can work to overcome these challenges and advance the care of patients.

中文翻译：

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质谱蛋白质组学方法在免疫球蛋白临床实验室中的应用


背景 临床实验室中的免疫球蛋白 （Ig） 测量传统上是通过比浊法、比浊法、电泳和 ELISA 测定法进行的。质谱 （MS） 测量有可能更深入地了解这些标志物的性质。内容 已经描述了不同的方法（自上而下、中而下或自下而上）用于测量内源性单克隆免疫球蛋白（M 蛋白）和外源性治疗性单克隆抗体疗法 （t-mAb） 的特异性 Ig。区分目标 Ig 与多克隆 Ig 背景存在挑战。MS 正在成为一种实用方法，可提供有关当前临床实验室方法不易确定的结构和克隆特征的定量分析和信息。本文讨论了临床实施的示例，包括 M 蛋白的分型和定量以及多克隆 Ig 背景下 t-mAb 的定量，作为 MS 如何增强我们对 Ig 的检测和表征的示例。总结：本综述对当前临床可用的 Igs MS 蛋白质组学检测的综述强调了实施过程中的分析和非分析挑战。鉴于从这些方法中对 Ig 有了新的见解，希望供应商、实验室、医疗保健提供者和支付系统能够努力克服这些挑战并推进对患者的护理。