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4.4.1. Total immunoglobulin assays

Chapter 4

Once a monoclonal protein has been identified in a serum sample, it is recommended that total immunoglobulins (IgG, IgA and IgM) are also measured by nephelometric/turbidimetric methods [136]. Whilst it is preferred that monoclonal proteins are monitored by densitometric quantification, in cases where small monoclonal proteins are obscured by other serum proteins (e.g. transferrin), nephelometric measurements may be more accurate [119][136]. However, total nephelometric measurements cannot discriminate between monoclonal and polyclonal immunoglobulins, which may limit their usefulness as the serum concentration approaches the normal range [37]. In their study of 149 patients with IgA MM, Katzmann et al. [38] showed that total IgA assays are less sensitive than IgA Hevylite assays for detection of monoclonal IgA in diagnostic and post-treatment samples (Table 4.4).

It is important that densitometric and nephelometric methods are not used interchangeably as they do not always yield the same result [119][136]. For example, nephelometry may overestimate high concentrations of monoclonal IgM, and will also overestimate monoclonal protein concentrations if samples contain significant levels of polyclonal immunoglobulin. Electrophoresis may underestimate high concentrations of IgG (possibly due to dye saturation, Section 17.5).