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Letters |
1 The Binding Site Ltd., PO Box 4073, Birmingham B29 6AT, UK
2 Department of Immunology, University of Birmingham, Birmingham B15 2TT, UK
aAuthor for correspondence.
To the Editor:
In a recent issue of this journal, Tate et al. (1) reported studies using assays for free immunoglobulin light chains (FLCs) that we have been instrumental in developing (2). Although in general agreement with their findings, we would like to highlight some additional data that are pertinent to several of their comments.
Tate et al. (1) concluded that more clinical data were required before the assays are adopted for routine clinical use. Since the acceptance of their report, however, several relevant studies have been published. Bradwell et al. (3) presented data showing that 224 of 224 patients with Bence Jones myeloma could be identified based on abnormal serum concentrations of FLCs at presentation, without the requirement for urine testing. They also demonstrated that serum FLC measurements were more sensitive than urine, presumably because of the kidney’s high capacity for protein catabolism. For the diagnosis of AL amyloidosis, Lachmann et al. (4) reported that serum FLC assays were more sensitive than electrophoresis or immunofixation of both serum and urine. Of 262 patients with primary amyloidosis, 257 had abnormal serum FLC concentrations, whereas only 207 had monoclonal proteins in their serum and/or urine detectable by immunofixation electrophoresis or protein electrophoresis (
2 = 45.19; P <0.0001). Changes in the concentrations of serum FLCs were also found to be the best marker for disease monitoring and prognosis. Preliminary results from a study at the Mayo Clinic indicate the existence of "free light chain monoclonal gammopathy of undetermined significance (MGUS)", which can be identified only by use of serum FLC assays (5).
Additional confirmation of all of these results is appropriate, and many additional studies are underway. All patients entered in the Medical Research Council, Myeloma IX trial and the Leukemia Research Fund/Cancer Research UK, MERIT trial, will have FLC measurements at entry and each follow-up attendance. However, current data are sufficiently compelling that FLC assays are used routinely in many centers worldwide for diagnosis and monitoring of AL amyloidosis, nonsecretory myeloma, and Bence Jones myeloma. The assays are in routine use here at Birmingham, with 277 nontrial patients currently being monitored.
We agree with Tate et al. (1) that the FLC assays should not be used in isolation for the diagnosis of myeloma. Preliminary analysis of data from our laboratories has indicated that FLC concentrations and ratios are within reference values in 
4% of patients with intact immunoglobulin multiple myeloma and in 40% of individuals with MGUS at the time of presentation (6). Our recommendation is for FLC assays to be run alongside serum electrophoresis. However, serum FLC assays may well be of value for monitoring multiple myeloma patients who secrete intact monoclonal immunoglobulins. The serum half-life of FLCs is much shorter than that of IgG (2–6 h vs 20 days); therefore, changes in FLC concentrations could provide an earlier measure of remission and a more rapid indication of the efficacy of treatment (6). In patients posttreatment, normalization of FLC concentrations and bone marrow biopsy results correlate, even when persisting intact immunoglobulin M-proteins suggest residual disease. This was also noted by Tate et al. (1).
Tate et al. (1) presented data regarding the quantitative performance of the FLC assays, and the results are broadly similar to our own assessments. However, any analysis of the performance of the FLC assays should be considered not only in the context of their demonstrated clinical utility but also in the context of the inadequacies of the current alternative methods for FLC quantification (7).
Acknowledgments
Drs. Mead and Carr-Smith are employed by The Binding Site, Professor Bradwell is a shareholder and chairman of the company, and The Binding Site developed, manufactures, and markets the FLC assays.
References
The following articles in journals at HighWire Press have cited this article:
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  E. S.K. Ma and E. T.K. Lee A Case of IgM Paraproteinemia in Which Serum Free Light Chain Values Were Within Reference Intervals Clin. Chem., February 1, 2007; 53(2): 362 - 363. [Full Text] [PDF]
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 M. Q. Lacy, W. J. Hogan, M. A. Gertz, A. Dispenzieri, S. V. Rajkumar, S. Hayman, S. Kumar, M. R. Litzow, and A. L. Schroeter Successful Treatment of Scleromyxedema With Autologous Peripheral Blood Stem Cell Transplantation Arch Dermatol, October 1, 2005; 141(10): 1277 - 1282. [Abstract] [Full Text] [PDF]
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