Performance and additional benefits of MALDI-TOF-MS in M-protein detection in plasma cell disorders

Mengmeng Dong1, Hongying Ye1, Xiao Xiao2

  • 1Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Annals of Medicine
|April 28, 2026
PubMed
Abstract

Insights

Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) offers a highly sensitive method for detecting monoclonal (M) proteins in plasma cell disorders. This advanced technique also identifies glycosylation and post-translational modifications, potentially correlating with treatment response.

Area of Science:

  • Clinical Chemistry
  • Mass Spectrometry
  • Oncology

Background:

  • Current monoclonal (M) protein detection methods like immunofixation electrophoresis (IFE), serum protein electrophoresis (SPEP), and serum free light chains (sFLC) have limitations in sensitivity and efficiency.
  • Plasma cell disorders (PCD) require accurate M-protein detection for diagnosis and monitoring.

Purpose of the Study:

  • To evaluate the performance and supplementary value of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) for M-protein detection.
  • To compare MALDI-TOF-MS with existing diagnostic methods for PCD.

Main Methods:

  • M-protein detection in 137 newly diagnosed PCD patients using MALDI-TOF-MS.
  • Comparison of MALDI-TOF-MS results against SPEP, IFE, and sFLC as the gold standard.
  • Confirmation of discrepant results using urine IFE.
  • Analysis of sensitivity for light chains (κ, λ) and heavy chains (IgG, IgA).

Main Results:

  • MALDI-TOF-MS demonstrated a high M-protein detection rate (98.5%) compared to SPEP (75.9%), serum IFE (86.9%), sFLC (71.5%), and urine IFE (76.0%).
  • The sensitivity of MALDI-TOF-MS for κ and λ light chains was 75.8% and 80.0%, respectively; for IgG and IgA, it was 93.5% and 65.5%.
  • MALDI-TOF-MS identified LC glycosylation in 17 patients and other post-translational modifications (PTMs) in 4 patients, with observed correlations between glycosylation changes and treatment response.

Conclusions:

  • MALDI-TOF-MS is a reliable tool for M-protein detection, offering high sensitivity and the capability to identify LC glycosylation and PTMs.
  • Observed correlations between abnormal peak changes detected by MALDI-TOF-MS and treatment response suggest its potential utility in monitoring therapy effectiveness.

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