John Mills, Ph.D., Discusses Mass Spectrometry-Based Analysis of M-proteins

According to a recent article in Clinical Laboratory Newsclinical laboratories are moving away from the traditional detection and measurement of monoclonal proteins (M-proteins) of using either gel or capillary zone electrophoresis, and moving to mass spectrometry applications. These applications have demonstrated potential for delivering greater analytical sensitivity and deeper insight into this disease process.

John Mills, Ph.D., a fellow in the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota, and author of this post, discusses the limits of the current methods, benefits of mass spectrometry, two approaches to use mass spectrometry, and steps to achieve wider adoption.

According to Dr. Mills, the gold standard for detecting M-protein, electrophoresis, suffers from several well-established limitations, including low analytical sensitivity, the inability to detect and accurately quantitate ß-migrating M-proteins, significant positive bias when quantitating M-proteins <0.2 g/dL, and variability in interpreting results across institutions. Electrophoretic methods can also be laborious, time-consuming, and difficult to automate.

Mass spectrometry can be a practical solution to electrophoresis’s limitations in measuring M-proteins due to the depth of insight it provides, enabling more personalized disease monitoring. In the article, Dr. Mills discusses two different applications of mass spectrometry for measuring M-proteins:

In the first, mass spectrometry serves as a potential replacement of current electrophoretic methods (gel or capillary zone electrophoresis and/or immunofixation/immunosubraction) such that a single mass spectrometry-based assay would substitute for M-protein identification, isotyping, and quantitation.

"In this case, the researchers sought to generate a robust, high throughput method that could overcome the analytical limitations of electrophoretic methods—as well as generate a cost-effective and automatable technology as compared to the current battery of tests used to screen, diagnose, and monitor patients," said Dr. Mills. They found that matrix assisted laser desorption ionization (MALDI) time-of-flight (TOF) MS improved sensitivity and the ability to detect and quantitate ß-migrating­ M-proteins while also reducing the number of tests necessary for patient management and bettering analytical times.

In the second application, investigators used mass spectrometry to detect residual disease in patients with a history of multiple myeloma who had received treatment and were subsequently found by electrophoretic methods to have undetectable disease.

The priority was maximizing sensitivity as well as providing accurate molecular mass measurements of M-proteins.

According to Dr. Mills, while preliminary work has highlighted the potential benefits of mass spectrometry-based approaches to analyze M-proteins, the journey to implementing this technology into clinical practice is just beginning. However, researchers have had success in showing that MALDI-TOF MS could potentially replace a decades old electrophoretic technique. "Now, with lower cost and more powerful instruments, proven cost savings, and literature reporting superior performance, MALDI-TOF is poised to become a standard practice in microbiology in the near future," stated Dr. Mills.

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Kelley Schreiber

Kelley Schreiber is a Marketing Channel Manager at Mayo Medical Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her new kitten, and exploring new foods.