Screening method for M-proteins in serum using nanobody enrichment coupled to MALDI-TOF mass spectrometry

Mindy C. Kohlhagen, David R. Barnidge, John R. Mills, Joshua Stoner, Kari M. Gurtner, Andrea M. Liptac, Denise I. Lofgren, Patrick M. Vanderboom, Angela Dispenzieri, Jerry A. Katzmann, Maria A.V. Willrich, Melissa R. Snyder, David L. Murray

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1345-1352
Number of pages8
JournalClinical chemistry
Volume62
Issue number10
DOIs
StatePublished - Oct 2016

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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    Kohlhagen, M. C., Barnidge, D. R., Mills, J. R., Stoner, J., Gurtner, K. M., Liptac, A. M., Lofgren, D. I., Vanderboom, P. M., Dispenzieri, A., Katzmann, J. A., Willrich, M. A. V., Snyder, M. R., & Murray, D. L. (2016). Screening method for M-proteins in serum using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clinical chemistry, 62(10), 1345-1352. https://doi.org/10.1373/clinchem.2015.253781