Measurement of Free Light Chains in Urine

Abstract

We read with interest the report by Bradwell et al. (1) describing a sensitive immunoassay for free light chains (FLCs) in serum and urine. We agree that sensitive and accurate immunoassays for FLCs can be useful in clinical laboratories for studying the renal handling of polyclonal FLCs in various conditions. We do not agree, however, that this type of assay can be used to detect Bence Jones protein (BJP) in serum or urine. The identity of BJP was established in 1962 as FLCs synthesized by a single clone of B cells (2). The product of a single clone of B cells is a unique protein with its own structural peculiarity of the variable region of the molecule. For a protein immunoassay to be accurate, the immunoreactivity of the antigen in the sample must be identical to the immunoreactivity of the antigen in the calibrator. In other words, a criterion for a valid immunoassay is that the dose response of the calibrator should parallel that of the serum or urine specimen. This is impossible to achieve in the measurement of a monoclonal protein that exhibits structural differences from the polyclonal light chains in the calibrator. The imbalance of antigenic determinants between polyclonal and monoclonal light chains makes methods susceptible to the risk of antigen excess. Problems of antigen excess occur, with even robust immunoassays for total light chains yielding falsely low light-chain concentrations and thus missing the diagnosis of potentially serious conditions such as light chain myeloma or … [↵][1]bAuthor for correspondence. Fax 44121-415-5163; e-mail a.r.Bradwell{at}bham.ac.uk. [1]: #xref-corresp-2-1