Serum Free Light Chain Measurements Move to Center Stage

For more than 150 years, the presence of Bence Jones protein [immunoglobulin free light chains (FLCs)] in the urine has been an important diagnostic marker for multiple myeloma. Indeed, it was the first cancer test, and 100 years before any others (1). Over the last few years, however, interest in FLCs has undergone a renaissance. Development of serum tests for free κ and free λ has opened the door to new applications and increased their clinical importance (2). By way of comparison, the management of diabetes mellitus was hugely improved when blood replaced urine for glucose analysis.The report by Katzmann et al. (3) in this issue of Clinical Chemistry adds valuable confirmatory data on serum FLC testing. It is the first report of the assays being used in routine clinics with analysis of results on 1020 samples. As the authors point out, the performance of the tests has matched up to the retrospective studies that have been published previously.From a physiologic viewpoint, blood tests for small proteins have clear advantages over urine tests. Serum FLCs are cleared rapidly through the renal glomeruli with a serum half-life of 2–6 h and are then metabolized in the proximal tubules of the nephrons. Under ordinary circumstances, little protein escapes to the urine (4), and serum FLC concentrations have to increase manyfold before the absorption mechanisms are overwhelmed. This makes urinalysis a fickle witness to changing FLC production. Conversion to a serum test provides clarity in assessing disease processes that were previously hidden from view.Serum concentrations of FLCs are dependent on the balance between production (by plasma cells and their progenitors) and renal clearance. When there is increased polyclonal immunoglobulin production and/or renal impairment, both κ and λ FLC concentrations can increase 10- to 20-fold. However, the relative concentration of κ …