Direct screening and quantification of monoclonal immunoglobulins in serum using MALDI-TOF mass spectrometry without antibody enrichment.

Objectives: Monoclonal gammopathies (MGs) are characterized by the presence of monoclonal immunoglobulins (M-proteins). Currently, recommendations for screening of MGs primarily rely on nephelometry, turbidimetry and electrophoresis, which have inherent limitations in sensitivity and throughput. This study aimed to evaluate a novel MALDI-TOF MS-based method, the intact M-protein Screening-Light Chain Assay (iMS-LC Assay), for direct M-protein detection and quantification without antibody enrichment.

Methods: Residual serum samples previously analyzed via serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) were reduced to dissociate light chains from heavy chains. MALDI-TOF MS was then performed to determine the presence of M-protein characteristic pattern. The iMS-LC Assay's analytical sensitivity, specificity, and screening efficacy in healthy populations were assessed.

Results: The iMS-LC Assay successfully detected all M-proteins identified by SPE and demonstrated higher sensitivity in analytical and diagnostic studies. It accurately quantified M-proteins at concentrations below 10 g/L, with a detection limit of 0.2 g/L and the ability to detect levels below 0.1 g/L. For samples with M-protein concentrations >1 g/L, intra-assay and inter-assay coefficients of variation were <10 %. In prospective screening of M-proteins in the healthy population, the iMS-LC Assay detected M-proteins at a prevalence of 3.15 %, higher than IFE (1.87 %) and SPE (0.94 %).

Conclusions: The iMS-LC Assay shows potential to replace SPE and drive advancements in the screening, diagnosis, and monitoring of MGs. Further validation of its clinical sensitivity and specificity is essential to determine its adequacy as a routine screening tool for M-proteins.