Performance evaluation of an automated mass spectrometry system for the measurement and isotyping of monoclonal immunoglobulins

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BACKGROUND: Monoclonal proteins are detected using electrophoretic techniques and used to help diagnose plasma cell dyscrasias. The Immunoglobulin Isotypes (GAM) for the EXENT® analyser (EXENT assay) is an automated MALDI-ToF mass spectrometry immunoassay, designed for use with Optilite® turbidimetric assays for the identification and measurement of monoclonal immunoglobulins (M-proteins). The assay reports M-protein presence, concentration, isotype, and mass/charge ratio (m/z). METHODS: The EXENT assay precision performance, linearity, lower limit of the measuring interval (LLMI) and interference were established per CLSI guidelines. M-proteins were evaluated using electrophoretic methods or the EXENT assay in clinical samples from 718 patients with various monoclonal gammopathies, 417 disease controls and 364 healthy samples at 3 different laboratories. RESULTS: The EXENT assay demonstrated a lower measuring limit of 0.308 g/L, 0.073 g/L and 0.054 g/L for IgG, IgA, and IgM in samples with normal polyclonal levels. Total imprecision ranged from 3.7 to 12.8% across all isotypes, and between-laboratory was 5.1-14.3%. Therapeutic monoclonal antibodies were flagged from endogenous IgG kappa M-proteins and showed no interference when m/z thresholds were met. Clinical cut-offs were established at 0.359 g/L (IgG), 0.325 g/L (IgA), and 0.197 g/L (IgM). The EXENT assay detected M-proteins in 92.6% of monoclonal gammopathy patients versus 85.1% by serum protein electrophoresis (SPE), with strong concentration correlations (r = 0.874) and 97% isotype concordance in positive samples. CONCLUSIONS: The EXENT assay demonstrated comparability to SPE and immunofixation electrophoresis (IFE) for M-protein detection and the evaluation of monoclonal gammopathies.