Paradigm Shift in Monoclonal Protein Detection: From Electrophoresis-based to Mass Spectrometry–based Methods
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Monoclonal protein (M-protein) is a crucial biomarker for diagnosing and monitoring mono- clonal gammopathies, including multiple myeloma (MM). Traditionally, electrophoresis (EP)-based methods, such as protein EP and immunofixation EP, have been widely used for M-protein detection. However, these methods can show low sensitivity and inadequate quantification of small amounts of M-protein. To overcome these challenges, EP-based methods are often combined with the quantification of serum free light chains in auto- mated immunoassays. Advances in mass spectrometry (MS) have introduced three main approaches for sample preparation: top-down, middle-down, and bottom-up. Middle-down approaches are commonly used with matrix-assisted laser desorption/ionization time-of- flight MS and liquid chromatography–electrospray ionization (LC–ESI) quadrupole time-of- flight MS, whereas the bottom-up approach is typically applied with LC–ESI Orbitrap MS. A review of studies, conducted from 2014 to 2024, on plasma cell disorders that utilized MS-based methods demonstrate improvements in the sensitivity and accuracy of M-pro- tein identification and quantification. MM remains the most frequently studied disease, with significant therapeutic advancements leading to improved outcomes. Minimal resid- ual disease has gained attention because of its correlation with better prognoses. Mono- clonal gammopathy of undetermined significance and amyloid light-chain amyloidosis are occasionally addressed, while studies on other rare diseases remain limited. This review highlights the clinical applications and advancements in MS-based methods, particularly in assessing M-protein levels for treatment responses, risk factors, and prognostic moni- toring. Given their advantages—high sensitivity and specificity, automation, cost-effective- ness, and time efficiency—MS-based methods may eventually replace EP-based methods in clinical laboratories.
Abstract
Monoclonal protein (M-protein) is a crucial biomarker for diagnosing and monitoring mono- clonal gammopathies, including multiple myeloma (MM). Traditionally, electrophoresis (EP)-based methods, such as protein EP and immunofixation EP, have been widely used for M-protein detection. However, these methods can show low sensitivity and inadequate quantification of small amounts of M-protein. To overcome these challenges, EP-based methods are often combined with the quantification of serum free light chains in auto- mated immunoassays. Advances in mass spectrometry (MS) have introduced three main approaches for sample preparation: top-down, middle-down, and bottom-up. Middle-down approaches are commonly used with matrix-assisted laser desorption/ionization time-of- flight MS and liquid chromatography–electrospray ionization (LC–ESI) quadrupole time-of- flight MS, whereas the bottom-up approach is typically applied with LC–ESI Orbitrap MS. A review of studies, conducted from 2014 to 2024, on plasma cell disorders that utilized MS-based methods demonstrate improvements in the sensitivity and accuracy of M-pro- tein identification and quantification. MM remains the most frequently studied disease, with significant therapeutic advancements leading to improved outcomes. Minimal resid- ual disease has gained attention because of its correlation with better prognoses. Mono- clonal gammopathy of undetermined significance and amyloid light-chain amyloidosis are occasionally addressed, while studies on other rare diseases remain limited. This review highlights the clinical applications and advancements in MS-based methods, particularly in assessing M-protein levels for treatment responses, risk factors, and prognostic moni- toring. Given their advantages—high sensitivity and specificity, automation, cost-effective- ness, and time efficiency—MS-based methods may eventually replace EP-based methods in clinical laboratories.