Mass spectrometry-based screening for monoclonal gammopathy in individuals undergoing routine physical examinations: Analyses of consecutive 15,068 cases in China.

BACKGROUND

The intact M-protein Screening-Light Chain Assay (iMS-LC Assay) is a MALDI-TOF mass spectrometry (MS)-based method for M-protein detection without antibody enrichment. This study evaluated its feasibility for M-protein screening in comparison with conventional serum protein electrophoresis (SPE).

METHODS

We prospectively enrolled 15,068 consecutive individuals aged ≥30 years undergoing routine physical examinations at Peking Union Medical College Hospital between December 2, 2024, and April 10, 2025. Residual serum samples from SPE were subjected to automated iMS-LC Assay screening. Samples positive by either MS or SPE underwent verification by serum immunofixation electrophoresis (IFE), free light chain (FLC) analysis, and MS isotyping.

RESULTS

MS screening identified 201 positive cases compared to 70 by SPE (p < 0.001), demonstrating consistently higher detection rates across all age groups and more than a threefold increase among individuals under 60. MS positivity rates increased with age: males 30-39y (0.44%), 40-49y (1.19%), 50-59y (1.60%), 60-69y (2.51%), 70-79y (7.56%), ≥80y (14.29%); females 30-39y (0.44%), 40-49y (1.10%), 50-59y (1.47%), 60-69y (2.46%), 70-79y (3.92%), ≥80y (8.00%).

CONCLUSION

The iMS-LC Assay demonstrated a higher detection yield than SPE for M-protein screening and identified additional low-abundance M-proteins, particularly in younger age groups.