False-Negative Results in Detection of Monoclonal Proteins by Capillary Zone Electrophoresis: A Prospective Study

Abstract

Over the last 5 years, capillary zone electrophoresis (CZE) with the use of fused-silica capillaries has been increasingly introduced in clinical laboratories for routine serum-protein electrophoresis (1). The multichannel, automated Paragon CZE 2000 instrument (seven capillaries in parallel; Beckman Coulter) represented an especially attractive alternative to time-consuming manual techniques. CZE has been documented to perform reliably for the analysis of serum proteins and for the detection of monoclonal components (2)(3). We reported (4) that the sensitivity of the Paragon CZE 2000 system for the detection of monoclonal components (93%) was superior to the sensitivity of cellulose acetate gel electrophoresis (74%) and agarose gel electrophoresis (86%). In a prospective study, Katzman et al. (5) reported sensitivities of 95% and 91% for seven-capillary electrophoresis and agarose gel electrophoresis, respectively. When compared with agarose gel electrophoresis, CZE was able to detect more low-concentration IgA monoclonal components or light chains that were hidden in agarose gel electrophoresis because of comigration with transferrin or C3 (6). Paraproteins that are missed by CZE are typically very low-concentration monoclonal components that are also missed by agarose gel electrophoresis, but not by immunofixation. Problems with the detection of monoclonal components by CZE have been described (7)(8). Using a single-capillary Beckman P/ACE instrument with a capillary and buffer different from the Paragon CZE 2000 system, Jenkins and Guerin (7) performed a prospective study on 5500 specimens in which they compared CZE with agarose gel electrophoresis for the detection of monoclonal components. The authors identified six paraproteins that did not separate correctly on CZE. On agarose gel electrophoresis, all of these proteins migrated in the very slow γ region. The pI …