title: Screening Method for M-Proteins in Serum Using Nanobody Enrichment Coupled to MALDI-TOF Mass Spectrometry.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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: Department of Laboratory Medicine and Pathology.
authors: Mindy C
authors: MC
authors: Kohlhagen
authors: Department of Laboratory Medicine and Pathology.
authors: David R
authors: DR
authors: Barnidge
authors: Department of Laboratory Medicine and Pathology.
authors: John R
authors: JR
authors: Mills
authors: Department of Laboratory Medicine and Pathology.
authors: Joshua
authors: J
authors: Stoner
authors: Department of Laboratory Medicine and Pathology.
authors: Kari M
authors: KM
authors: Gurtner
authors: Department of Laboratory Medicine and Pathology.
authors: Andrea M
authors: AM
authors: Liptac
authors: Department of Laboratory Medicine and Pathology.
authors: Denise I
authors: DI
authors: Lofgren
authors: Medical Genome Facility-Proteomics Core, Mayo Clinic, Rochester, MN.
authors: Patrick M
authors: PM
authors: Vanderboom
authors: Division of Hematology, Department of Medicine, and.
authors: Angela
authors: A
authors: Dispenzieri
authors: Department of Laboratory Medicine and Pathology.
authors: Jerry A
authors: JA
authors: Katzmann
authors: Department of Laboratory Medicine and Pathology.
authors: Maria A V
authors: MA
authors: Willrich
authors: Department of Laboratory Medicine and Pathology.
authors: Melissa R
authors: MR
authors: Snyder
authors: Department of Laboratory Medicine and Pathology, murray.david@mayo.edu.
authors: David L
authors: DL
authors: Murray
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood* / Q000276:immunology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood* / Q000276:immunology; D053758:Nanoparticles / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000911:Antibodies, Monoclonal; D007147:Immunoglobulin Light Chains