In contrast, UPEP is much more sensitive for picking up light chain-producing myelomas. Free urine light chains, also called Bence-Jones proteins, are more readily picked up due to the lower protein concentration in urine, which allows for greater sample concentration. Urine proteins can also be fixed by soluble antibodies for further analysis (UIFE).
How are myelomas that do not secrete light or heavy chains (nonsecretory myelomas, about 3% of total cases) detected? Recently, it has been shown that almost 70% produce detectable levels of serum free light chains (SFLCs). Serum free light chains are detect using an antibody raised against a unique epitope on kappa and lambda light chains that are exposed only on light chains not bound to Igs. SFLCs have also been shown to be more sensitive than UPEP in detecting light chain secretory myelomas: in one series, 25% of patients with light chain MM had positive M spikes on UPEP, versus 54% with positive SFLC tests. The increased sensitivity of SFLCs may be attributable to renal proximal tubular absorption of light chains, lowering their concentration in the urine (and on UPEP).
Are there any disadvantages to the SFLC assay? Two identified by the International Myeloma Working Group include variability of 10-20% between lots of the antibody, and falsely low SFLC levels in states of antigen excess. To my surprise, SFLC tests are not prohibitively expensive: Katzmann et al estimated that SFLCs are about half the cost of UPEP/UIFE assays.
It seems there is a strong case for ordering SFLCs in our patients with renal disease suspected of having a monoclonal gammopathy. I would be curious to know whether other institutions are using it for screening, and their experiences. Renal function needs to taken into account when interpreting SFLCs (kappa light chains are cleared more than lambda). Resulting in a ratio of 0.6 at baseline. This was reviewed by Finnian here.