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

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.