Applications of Mass Spectrometry Proteomic Methods to Immunoglobulins in the Clinical Laboratory

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.