Serum free light chain analysis may miss monoclonal light chains that urine immunofixation electrophoreses would detect

Background: A nephelometric assay for identifying free light chains (FLC) of immunoglobulin in serum is commercially available. Although this assay is not specific for monoclonal FLC, an abnormal kappa/lambda ratio is thought to presumptively identify monoclonal FLCs. It has been proposed that serum FLC assays can replace urine immunofixation electrophoresis (IFE) for routine detection. This proposal seems to be based upon testing of samples retrospectively drawn from patients mostly with myeloma or known primary amyloidosis-conditions that are less frequently observed in general laboratory practice. Methods: Prospective analysis of 5 patient samples by standard care techniques with serum/urine IFE compared with serum FLC nephelometric assay. Rather than classical myeloma, cases were selected on the basis of unusual or equivocal atypical serum protein electrophoresis patterns. Results: In all 5 cases, the nephelometric method for free light chains was negative by virtue of serum FLC kappa/lambda ratio being within the reference range, contrasting with monoclonal proteins or free light chains detected by serum/urine IFE. Conclusions: Since peculiar or unusual patterns are more commonly observed in general practice, these cases illustrate the pitfalls of relying solely on the serum free light chain analysis method in order to establish the presence of monoclonal FLC. Published by Elsevier B.V.