23.4. The sensitivity of abnormal sFLC ratios for Bence Jones proteinuria

Chapter 23

As indicated in the IMWG guidelines [167], the logical use of sFLC analysis in screening is as a replacement for urinalysis, and a number of studies have directly analysed the sensitivity of serum assays for identifying patients with urinary Bence Jones protein (uBJP). The largest study is discussed above (Section 23.2) and reported that serum tests (including sFLC) identified almost all patients requiring medical intervention, with the exception of some patients with AL amyloidosis [134].

Results from other studies have also reached this conclusion: Hill et al. reported 15 patients with uBJP, of whom 12 were detected by SPE plus sFLC [163]. The remaining three patients all had uBJP concentrations measured at ~50mg/L, and only 1 of these had persistent uBJP; however, as a skeletal survey and bone marrow biopsy were negative, this was consistent with a diagnosis of FLC-only MGUS. Beetham and colleagues [187] concluded that uIFE should still be included in a screening algorithm, but of the 34 patients found to have uBJP in their screening study, 26 had abnormal κ/λ ratios, and of the remaining eight, only one MGUS patient (with uBJP <50 mg/L) did not have a serum monoclonal protein identified.

Finally, Holding et al. [188] reviewed 126 patients who had a newly diagnosed monoclonal gammopathy with uBJP and found that 124 had abnormal sFLC results, while the remaining 2 also had IgGκ paraproteins detected by SPE, so serum analysis would have identified all 126 cases. Holding et al. [188] also presented a detailed review of similar studies, highlighting how the use of concentrated versus unconcentrated urine or uIFE versus UPE (as an initial test) would have influenced the results. In addition, it was also noted that when uBJP had been identified in patients with normal sFLC ratios, the concentration of urinary FLC determined by electrophoretic methods was always low, indicating that the discrepant results were unlikely to have been caused by the polyclonal antibodies (in the sFLC assays) failing to recognise the patients’ FLCs (Section 24.9).