BACKGROUND: Current recommendations for screening for monoclonal gammopathies include serum protein electrophoresis (PEL), imunofixation electrophoresis (IFE), and free light chain (FLC) ratios to identify or rule out an M-protein. The aim of this study was to examine the feasibility of an assay based on immunoenrichment and MALDI-TOF-MS (MASS-SCREEN) to qualitatively screen for M-proteins. METHODS: Serum from 556 patients previously screened for M-proteins by PEL and IFE were immunopurified using a κ/λ-specific nanobody bead mixture. Following purification, light chains (LC) were released from their heavy chains by reduction. MALDI-TOF analysis was performed and the mass-to-charge LC distributions were visually examined for the presence of an M-protein by both unblinded and blinded analysts. RESULTS: In unblinded analysis, MASS-SCREEN detected 100% of the PEL-positive samples with an analytical sensitivity and specificity of 96% and 81% using IFE positivity as the standard. In a blinded analysis using 6 different laboratory personnel, consensus was reached in 92% of the samples. Overall analytical sensitivity and specificity were reduced to 92% and 80%, respectively. FLC ratios were found to be abnormal in 28% of MASS-SCREEN-negative samples, suggesting FLC measurements need to be considered in screening. CONCLUSIONS: MASS-SCREEN could replace PEL in a panel that would include FLC measurements. Further studies and method development should be performed to validate the clinical sensitivity and specificity and to determine if this panel will suffice as a general screen for monoclonal proteins.
BACKGROUND: Current recommendations for screening for monoclonal gammopathies include serum protein electrophoresis (PEL), imunofixation electrophoresis (IFE), and free light chain (FLC) ratios to identify or rule out an M-protein. The aim of this study was to examine the feasibility of an assay based on immunoenrichment and MALDI-TOF-MS (MASS-SCREEN) to qualitatively screen for M-proteins. METHODS: Serum from 556 patients previously screened for M-proteins by PEL and IFE were immunopurified using a κ/λ-specific nanobody bead mixture. Following purification, light chains (LC) were released from their heavy chains by reduction. MALDI-TOF analysis was performed and the mass-to-charge LC distributions were visually examined for the presence of an M-protein by both unblinded and blinded analysts. RESULTS: In unblinded analysis, MASS-SCREEN detected 100% of the PEL-positive samples with an analytical sensitivity and specificity of 96% and 81% using IFE positivity as the standard. In a blinded analysis using 6 different laboratory personnel, consensus was reached in 92% of the samples. Overall analytical sensitivity and specificity were reduced to 92% and 80%, respectively. FLC ratios were found to be abnormal in 28% of MASS-SCREEN-negative samples, suggesting FLC measurements need to be considered in screening. CONCLUSIONS: MASS-SCREEN could replace PEL in a panel that would include FLC measurements. Further studies and method development should be performed to validate the clinical sensitivity and specificity and to determine if this panel will suffice as a general screen for monoclonal proteins.
Authors: Lidong He; Lissa C Anderson; David R Barnidge; David L Murray; Christopher L Hendrickson; Alan G Marshall Journal: J Am Soc Mass Spectrom Date: 2017-02-28 Impact factor: 3.109
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Authors: Noemí Puig; María-Teresa Contreras; Cristina Agulló; Joaquín Martínez-López; Albert Oriol; María-Jesús Blanchard; Rafael Ríos; Jesús Martín; María-Belén Iñigo; Anna Sureda; Miguel-Teodoro Hernández; Javier de la Rubia; Verónica González-Calle; Isabel Krsnik; Valentín Cabañas; Luis Palomera; José-María Moraleda; Joan Bargay; María-Teresa Cedena; Bruno Paiva; Laura Rosiñol; Joan Bladé; Jesús San Miguel; Juan-José Lahuerta; María-Victoria Mateos Journal: Blood Adv Date: 2022-06-14
Authors: David L Murray; Noemi Puig; Sigurdur Kristinsson; Saad Z Usmani; Angela Dispenzieri; Giada Bianchi; Shaji Kumar; Wee Joo Chng; Roman Hajek; Bruno Paiva; Anders Waage; S Vincent Rajkumar; Brian Durie Journal: Blood Cancer J Date: 2021-02-01 Impact factor: 11.037