11.5.1. Comparison of Hevylite and total immunoglobulin measurements

Chapter 11

In general, the agreement between summated Hevylite (e.g. IgGκ + IgGλ) and total immunoglobulin assays (e.g. IgG) is good; indeed, comparison of summation data was used to validate the assays during development and summation checks are used as part of the manufacturing quality control (Sections 9.4.4 and 9.7). Eckold et al. [895] compared summated IgG, IgA and IgM HLC concentrations with total immunoglobulins and reported an excellent linear correlation (Figure 11.3). Theoretically, the more a tumour suppresses the production of polyclonal immunoglobulin (of the same immunoglobulin class), the closer will be the correspondence between iHLC concentrations with both the total immunoglobulin concentrations and the monoclonal immunoglobulin concentrations, as measured by densitometry of SPE gels.

As part of an evaluation of HLC assays for monitoring multiple myeloma (MM) patients, Katzmann et al. [38] compared total IgA quantification and the IgA iHLC for 149 IgA MM samples. Passing–Bablok linear regression gave a slope of 1.124 (95% CI 1.015–1.194), r = 0.969 Figure 11.4A), indicating a good agreement. A further study by the same group [969] compared summated Hevylite with total immunoglobulins for 518 IgG and IgA MM patients at diagnosis. A total of 254/518 (49%) of summated Hevylite values fell outside the recovery range (defined as 80 – 120% total immunoglobulin values). Despite repeating 254 measurements, only one sample (an IgAκ) demonstrated Hevylite antigen excess (Section 11.4).

Boyle et al. [901] compared total IgM and summated IgM HLC values (IgMκ + IgMλ) for sera from 110 normal donors and 78 Waldenström’s macroglobulinaemia (WM) patients. There was a good correlation between the results (Linear regression R2 = 0.90, Passing-Bablok regression y=-0.32 + 1.17x, Figure 11.5A), although Bland-Altman analysis demonstrated that IgM values measured using IgM Hevylite assays were slightly higher than those measured using total IgM assays (bias = 1.8 g/L, Figure 11.5B). Similar findings were reported by Manier et al. [681] and Sarto et al. [936].