Serum free light chain reference intervals in an Optilite and their influence on clinical guidelines.

Background: Serum free light chain (FLC) analysis has been incorporated into the International Myeloma Working Group guidelines for the diagnosis and management of all monoclonal gammopathies. These recommendations were solely based on a single assay method (Freelite assay) and instrument. Here, we establish new reference intervals (RIs) for kappa and lambda FLC and the kappa-lambda difference and sum and a new diagnostic range for kappa/lambda FLC ratio (K/L-FLC) in an Optilite turbidimeter (The Binding Site) with the Freelite assay.

Methods: To establish new RIs, the CLSI EP28-A3C protocol was applied to 249 sample blood donors from Fuenlabrada, Spain, and the central 95% and total range were estimated. Samples from patients with polyclonal hypo- and hypergammaglobulinemia were used for the evaluation of K/L-FLC as a monoclonal proliferation index.

Results: The new RIs and the new K/L-FLC diagnostic range for the Optilite (0.65-2.56 mg/L) are very different from those in on the guidelines (0.26-1.65 mg/L). We propose new RIs for the K - L difference and the K + L sum. Diagnostic range validation as a monoclonal proliferation index with samples with hypo- and hypergammaglobulinemia confirms this new range.

Conclusions: In this study, we present the FLC RI for Freelite reagents measured on an Optilite turbidimeter. These ranges are different from those provided by the manufacturer and from those used in most studies in the literature, which may lead to patient misclassification. Manufacturers and clinical laboratories must strive to provide RIs for the technology they are using and for their population.