4.4.2. Total κ/λ assays

Chapter 4

Nephelometric total light chain assays measure the concentration of all intact immunoglobulin and FLCs of a particular light chain type (e.g. total κ assays measure IgGκ + IgAκ + IgMκ + IgDκ + IgEκ + κ sFLCs). Results are expressed as a κ/λ ratio and are used by some laboratories as a screen for monoclonal gammopathy. However, it is an insensitive approach. The presence of background polyclonal immunoglobulins prevents the detection of monoclonal proteins smaller than around 4 g/L [128].

In the largest study to date, Hungria et al. [871] compared the diagnostic sensitivity of Freelite sFLC assays and total κ and λ assays (Beckman Coulter) in 114 patients with light chain MM (LCMM). At diagnosis, the sFLC assay identified clonality in 11/11 samples, compared to 2/11 for the total light chain assay (Figure 4.5). During follow-up, an abnormal κ/λ sFLC ratio indicated monoclonal sFLCs in 80/103 samples, compared to 25/103 for the total light chain assay (Figure 4.5). Confusingly, the total light chain assay misreported the monoclonal light chain type in 11 samples.

Marien et al. [139] compared the diagnostic performance of the sFLC and total light chain assays using sera from 16 LCMM patients. All samples were abnormal by sFLC assays (Figure 4.6). This compared with only five of the 16 samples by total κ and λ assays, and one λ patient was mistyped as κ. Other studies have confirmed that total light chain assays are less sensitive than sFLC analysis for the diagnosis of LCMM, nonsecretory MM (NSMM) and AL amyloidosis [145][141] and for screening for MM [913]. Thus, the benefits of the total κ/λ assays are limited, and they are not recommended by international guidelines (Chapter 25) [142].