An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part I: factors impacting limit of quantitation of serum protein electrophoresis
| Autor: | David F. Keren, Jody L. Frinack, Katherine A Turner, Martina Zaninotto, Anna Caldini, Michael W Ettore, Stephen Bell, Galina Zemtsovskaja, Robert O. Fullinfaw, Gabriella Righetti, Sara Altinier, Maria Stella Graziani, Christopher R. McCudden, Katina Katakouzinos, Matthew Burke, Julio C. Delgado, Marie Therese Melki, Ronald A. Booth, Joannes F M Jacobs, Maria Alice V. Willrich, Jillian R Tate, Theo de Malmanche, Giovanni Palladini |
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| Rok vydání: | 2020 |
| Předmět: |
Immunofixation
Accuracy and precision monoclonal proteins limit of quantitation Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] Clinical Biochemistry Paraproteinemias Antibodies Monoclonal Humanized immunosubtraction All institutes and research themes of the Radboud University Medical Center Limit of Detection medicine Humans Detection limit Chromatography biology medicine.diagnostic_test accuracy Chemistry Biochemistry (medical) immunofixation Hypergammaglobulinemia protein electrophoresis Antibodies Monoclonal Reproducibility of Results Gamma globulin General Medicine Gel electrophoresis of proteins medicine.disease Blood Protein Electrophoresis Laboratories Hospital Immunoglobulin Isotypes Myeloma Proteins Serum protein electrophoresis Monoclonal biology.protein |
| Zdroj: | Clinical Chemistry and Laboratory Medicine, 58, 533-546 Clinical Chemistry and Laboratory Medicine, 58, 4, pp. 533-546 |
| ISSN: | 1434-6621 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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