Quantitation of serum free light chains does not compensate for serum immunofixation only when screening for monoclonal gammopathies

Abstract

Background: Detection of plasma cell dyscrasias (PCD) requires screening of serum and urine for monoclonal proteins. Several studies have demonstrated increased sensitivity and specificity when measurement of serum free light chain (SFLC) is part of the screening protocol. In addition, omission of immunofixation (IFE) in the standard work-up that includes SFLC assay has been proposed. This study attempts to define the role of the SFLC assay in a screening strategy limited to serum only. It compares outcomes to a serum-only screening strategy that omits serum IFE. Methods: Serum from 691 patients was analysed for the presence of monoclonal protein using standard serum IFE, serum protein electrophoresis (SPE) and measurement of SFLC. Data were analysed retrospectively. Results: Specificity and sensitivity of abnormal SFLCratios for the detection of monoclonal protein using IFE were 96% and 41%, respectively. Eighteen patients with negative monospecific and Bence Jones IFE, but abnormal SFLC-ratios were identified. In most cases, this could be attributed to kidney and inflammatory disease or haematological disorders. In four cases, this resulted in further diagnostic investigation and light chain disease was later detected in two cases. Light chain disease was confirmed in one case but not confirmed in the other patient. In 14 patients, Bence Jones IFE was negative, although the concentrations of SFLC suggested the presence of monoclonal Bence Jones protein at concentrations detectable by IFE. Thus, either the anti-serum failed at detection, there was polymerisation of the free light chains or the SFLC assay overestimated protein concentrations. Simulating a work-up that included IFE only if abnormalities were detected by SPE or the SFLC assay would have resulted in 26% fewer IFEs being performed, but three patients with monoclonal proteins by IFE would have been missed. Conclusions: Abnormal SFLC concentrations are neither sensitive nor specific for the detection of

Understanding the Constraints and Optimization of Serum Immunofixation Electrophoresis and Serum Free Light Chains for Detecting Monoclonal Proteins: A Single-Center Experience

“…2 Several studies have upheld the use of combination or sequential tests for accurate diagnosis owing to the discrepant results of SFLC vis-a-vis electrophoresis. 3,17,[21][22][23]25,26 In the current study, we encountered 28.9% discordance between SIFE and SFLC results. Since normal SFLC ratio heralds an impending negative SIFE, we propose a more practical laboratory-based approach to follow-up MM patients.…”

“…According to Böer and Deufel, not just MM but non-neoplastic conditions such as infections, autoimmune disorders, chronic liver disease, and neurological disorders as well as certain malignancies produce hypergammaglobulinemia or elevated serum levels of κ and λ. 21 Bhole et al and Heaton et al attributed issues such as excess antigen, nonlinear antigen-antibody reaction, and polymerization of FLC molecules, which lead to falsely elevated or diminished values of SFLC. 22,23 Associated renal dysfunction and aggregator property of SFLC can also yield erroneous results which do not correspond to SIFE as mentioned by Singh.…”

The Evaluation of Distal Symmetric Polyneuropathy

“…Neurologists are much more likely to order both tests, while internists rarely order an immunofixation test. The SPEP alone is much less sensitive than when done in conjunction with an immunofixation, and therefore, both tests should be performed when there is suspicion of an underlying bone marrow disorder 23–25 . Evidence exists that patients with neuropathy have an increased prevalence of abnormal SPEP results especially in those with demyelinating neuropathy 26 .…”