11.5.3. Comparison of Hevylite and immunofixation electrophoresis

Chapter 11

In general, the concordance between the M-protein type determined by Hevylite and immunofixation electrophoresis (IFE) is very good [127][1062][1065][1064][1067]. A number of studies have shown excellent agreement at diagnosis of MM (Section 17.6) and Waldenström’s macroglobulinaemia (Section 32.4.1). Other groups have compared Hevylite and IFE in a range of samples submitted for routine serum electrophoresis [1062][1065]. For example, Jacobs at al. [1065] compared the M-protein type determined by Hevylite and IFE in 166 routine clinical samples, as well as 27 samples from patients with known monoclonal gammopathy. They demonstrated high concordance (Cohen κ coefficient of 0.84) between both methods, and 93% of tested samples had identical results. Similar results were reported by Paoloni et al. [1062].

Occasionally, discrepancies occur between Hevylite and immunofixation results during follow-up of patients with monoclonal gammopathies. These can be broadly grouped into two scenarios, which are discussed below.

1) IFE positive, normal HLC ratio: in IgG patients, recycling of IgG by the FcRn receptor may result in the persistence of small IgG monoclonal proteins in the serum, causing IFE to remain positive long after the tumour has been eradicated and HLC pair suppression has ended (Section 18.4.5). In addition, in a minority of cases, the diagnostic sensitivity of IFE may be superior to that of the HLC ratio. For example, if a small IgG monoclonal protein is present with a large amount of polyclonal IgG [40]. Finally, on rare occasions, Hevylite antigen excess may cause a sample value to be falsely low. If antigen excess is suspected, an additional sample dilution should be performed (Section 11.4).

2) IFE negative, abnormal HLC ratio: in some patients, the HLC ratio may be more sensitive for detecting a monoclonal immunoglobulin than IFE. This is more common for IgA and IgM where there is less polyclonal production so smaller amounts of monoclonal immunoglobulin can produce an abnormal HLC ratio [127]. An abnormal HLC ratio may indicate residual disease in IIMM patients whose electrophoresis results have normalised following therapy (Section 18.4.3).