Detection and typing of paraproteins: comparison of different methods in a routine diagnostic laboratory

In this paper we review four methods: Protein electrophoresis (PE), immunoelectrophoresis (IEP), immunofixation electrophoresis (IFE) and a nephelometric kappa:lambda ratio method for the ability, first, to detect, and second, to isotype paraproteins in urine and serum. IFE was the most sensitive assay both in the detection of paraproteins and the most accurate in their typing. The nephelometric kappa:lambda ratio was associated with false-positive and false-negative results and cannot be considered suitable for routine diagnostic use. Although IFE was the most sensitive assay it was not without problems. Dilution of the serum to produce a concentration suitable for IFE is critical, and the assay is demanding in operator skill and time. The extra paraproteins identified by IFE are generally of low concentration and with the exception of certain well-defined clinical situations are probably not of great importance in patient management. In the case of diseases where the demonstration of a small amount of paraprotein is important, such as amyloidosis, then IFE should be performed in case other techniques fail to demonstrate a paraprotein. Otherwise, IFE is best reserved for paraproteins detected by PE which cannot be typed by IEP. A schema for the management of paraprotein identification for use in a routine diagnostic laboratory is presented.