Interpreting Free Light Chain Screening Studies
There are two papers that show a number of false negative results for the serum light chain ratio (LCR) when compared with urine protein electrophoresis in a serum and urine screening setting1, 2. The false negative rates in these papers, after removing those that had normal electrophoresis on a repeat sample were 8%1 and 21%2, which are comparable with the rate of about 7% found in retrospective studies of selected positive samples. The higher rate in the above two studies was found when all urines were fixed2, as opposed to selective fixation based on the electrophoresis findings in the other study1. However, the curious finding is that these were all very low levels of urine light chain (generally <100 mg/L) and in most cases corresponded with the isotype of an intact immunoglobulin MGUS or myeloma in the patient's serum. If there was a general problem with the Freelite™ assay missing serum light chains of particular restricted epitope expression, it would be expected that the concentrations found in the urine of these patients would vary widely and include some high levels, but there is only one record in the literature of a demonstrable missed epitope3, a problem now corrected4. This suggests that the source of the urinary light chains in these patients is probably not serum, but rather the product of some process occurring in the kidney and involving the breakdown of intact monoclonal paraproteins in selected patients. This is supported by the high sensitivity of the assays for light chain myeloma and AL amyloid, in which the false negative results do not seem to be an issue (summarised by Jagannath et al5). It will be interesting to see the results of larger studies of the assay in routine practice, including longer term follow up of these patients.
Dr Stephen Holding
Principal Clinical Scientist
Honorary Clinical Senior Lecturer
Immunology Department
Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
Reference List
1. Hill PG, Forsyth JM, Rai B, Mayne S. Serum free light chains: an alternative to the urine Bence Jones proteins screening test for monoclonal gammopathies. Clin Chem 2006; 52(9):1743-1748.
2. Beetham R, Wassell J, Wallage MJ, Whiteway AJ, James JA. Can serum free light chains replace urine electrophoresis in the detection of monoclonal gammopathies? Ann Clin Biochem 2007; 44(Pt 6):516-522.
3. Tate JR, Mollee P, Dimeski G, Carter AC, Gill D. Analytical performance of serum free light-chain assay during monitoring of patients with monoclonal light-chain diseases. Clin Chim Acta 2007; 376(1-2):30-36.
4. Robson E, Mead G, Carr-Smith H, Bradwell A. In reply to Tate et al. Clin Chim Acta 2007;376:30-6. Clin Chim Acta 2007; 380(1-2):247-1.
5. Jagannath S. Value of serum free light chain testing for the diagnosis and monitoring of monoclonal gammopathies in hematology. Clin Lymphoma Myeloma 2007; 7(8):518-523.
