Work

A non-affinity-dependent high-resolution mass spectrometry method for detecting and typing monoclonal free light immunoglobulin chains

Year: 2025

Type: article

Abstract: Background: Detecting and monitoring monoclonal free light immunoglobulin chains in serum is important for managing patients with B-cell neoplasms. Established methods have relied on immunochemistry, with monoclonality determined through an abnormal ratio of free kappa and lambda chains and an increased concentration of the involved chain. This indirect approach has limitations. Mass spectrometric methods that directly demonstrate the monoclonal fraction have been described; however, all reported approaches so far are affinity-dependent. The aim of this study was to develop a non-affinity-dependent high-resolution mass spectrometry (HRMS) method. Methods: Samples were prepared using ultrafiltration, then separated by reversed-phase liquid chromatography and analyzed by HRMS. The performance of the method was evaluated, including a comparison with a nephelometric immunoassay for free light immunoglobulin chains. Results: Concordance between HRMS and the immunoassay in classifying a sample as containing a monoclonal free light chain or not was 84% (based on 100 unique patient samples). HRMS identified more samples containing a monoclonal free light chain than the immunoassay. Some monoclonal fractions were glycosylated and/or cysteinylated. Imprecision (CV) for the concentration measurements of monoclonal fractions ranged from 10 to 14%. Conclusions: The HRMS method presented can detect, isotype, and semi-quantify monoclonal monomeric and dimeric light chains in serum, as well as demonstrate post-translational modifications. It is a selective, non-affinity-dependent method with a simple workflow that has the potential to become a valuable tool in the management of B-cell diseases.

Source: Journal of Mass Spectrometry and Advances in the Clinical Lab

DOI: 10.1016/j.jmsacl.2025.11.004

Authors: Per Bengtson, Magnus Förnvik Jonsson

Institutions: Hallands sjukhus Halmstad, Lund University, Skåne University Hospital

Language: English

Topic: Multiple Myeloma Research and Treatments

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $900