Mass Spectrometry Transforms Clinical Immunoglobulin Analysis and M-Protein Detection
This review covers the emerging application of mass spectrometry to clinical immunoglobulin measurement, offering deeper characterization than traditional nephelometry, electrophoresis, and ELISA. MS-based approaches enable isotyping, quantification, and clonal tracking of monoclonal proteins as well as monitoring therapeutic monoclonal antibodies within polyclonal backgrounds. The authors discuss both the analytical advantages and the implementation challenges that laboratories, vendors, and payers must address.
The original study
Applications of Mass Spectrometry Proteomic Methods to Immunoglobulins in the Clinical Laboratory.
- Authors
- Murray DL, Willrich MAV
- Journal
- Clinical chemistry
- Type
- Journal Article, Review
- PMID
- 39667030
Original abstract
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.