Abstract
Background Serum protein electrophoresis (SPEP) is used to quantify the serum monoclonal component or M-protein, for diagnosis and monitoring of monoclonal gammopathies. Significant imprecision and inaccuracy pose challenges in reporting small M-proteins. Using therapeutic monoclonal antibody-spiked sera and a pooled beta-migrating M-protein, we aimed to assess SPEP limitations and variability across 16 laboratories in three continents. Methods Sera with normal, hypo- or hypergammaglobulinemia were spiked with daratumumab, Dara (cathodal migrating), or elotuzumab, Elo (central-gamma migrating), with concentrations from 0.125 to 10 g/L (n = 62) along with a beta-migrating sample (n = 9). Provided with total protein (reverse biuret, Siemens), laboratories blindly analyzed samples according to their SPEP and immunofixation (IFE) or immunosubtraction (ISUB) standard operating procedures. Sixteen laboratories reported the perpendicular drop (PD) method of gating the M-protein, while 10 used tangent skimming (TS). A mean percent recovery range of 80%-120% was set as acceptable. The inter-laboratory %CV was calculated. Results Gamma globulin background, migration pattern and concentration all affect the precision and accuracy of quantifying M-proteins by SPEP. As the background increases, imprecision increases and accuracy decreases leading to overestimation of M-protein quantitation especially evident in hypergamma samples, and more prominent with PD. Cathodal migrating M-proteins were associated with less imprecision and higher accuracy compared to central-gamma migrating M-proteins, which is attributed to the increased gamma background contribution in M-proteins migrating in the middle of the gamma fraction. There is greater imprecision and loss of accuracy at lower M-protein concentrations. Conclusions This study suggests that quantifying exceedingly low concentrations of M-proteins, although possible, may not yield adequate accuracy and precision between laboratories.
Highlights
This study suggests that quantifying exceedingly low concentrations of M-proteins, possible, may not yield adequate accuracy and precision between laboratories
Founded on the secretion of a monoclonal immunoglobulin (M-protein), plasma cell proliferative disorders are classified as monoclonal gammopathies and include multiple myeloma (MM), Waldenström’s macroglobulinemia (WM), amyloidosis (AL), light chain deposition disease (LCDD), POEMS syndrome, and premalignant diseases such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM)
Due to the wide range of disease presentations, identification of the M-protein by serum protein electrophoresis (SPEP) may be the first clue to the diagnosis of a monoclonal gammopathy followed by subsequent isotyping via immunofixation (IFE) or immunosubtraction (ISUB)
Summary
Founded on the secretion of a monoclonal immunoglobulin (M-protein), plasma cell proliferative disorders are classified as monoclonal gammopathies and include multiple myeloma (MM), Waldenström’s macroglobulinemia (WM), amyloidosis (AL), light chain deposition disease (LCDD), POEMS syndrome, and premalignant diseases such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Due to the wide range of disease presentations, identification of the M-protein by serum protein electrophoresis (SPEP) may be the first clue to the diagnosis of a monoclonal gammopathy followed by subsequent isotyping via immunofixation (IFE) or immunosubtraction (ISUB). SPEP and IFE/ISUB are indispensable clinical assays for the diagnosis, risk stratification and therapeutic m onitoring of monoclonal gammopathies [1,2,3]. Methods: Sera with normal, hypo- or hypergammaglobulinemia were spiked with daratumumab, Dara (cathodal migrating), or elotuzumab, Elo (central-gamma migrating), with concentrations from 0.125 to 10 g/L (n = 62) along with a beta-migrating sample (n = 9). Results: Gamma globulin background, migration pattern and concentration all affect the precision and accuracy of quantifying M-proteins by SPEP. There is greater imprecision and loss of accuracy at lower M-protein concentrations
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