Serum free light chain reference values: A critical approach.

OBJECTIVES: The clinical usefulness of serum free light chain (FLC) measurement in the management of patients with plasma cell proliferative disorders has been reported in several papers, and most clinical studies use the reference ranges declared by the manufacturer. The aim of the present study was to evaluate the reproducibility of FLCs immunoassay and to validate the reference range, before introducing it in routine setting. DESIGN AND METHODS: Internal quality control materials and a pool of fresh serum samples were used to evaluate imprecision; 162 fresh sera from healthy blood donors were analyzed to evaluate the reference range for FLCs. In order to verify the \u3ba/\u3bb FLC ratio, 43 sera from patients with polyclonal hypergammaglobulinemia were tested. The FLC immunoassay was performed using a nephelometer with the Freelite reagents. RESULTS: The imprecision studies performed using a serum pool tested with two different lots of reagents showed a mean CV of 16.09% for \u3baFLC and of 16.72% for \u3bbFLC. Lower CV%s and different mean values were found by calculating the results from each specific lot separately, while different results were obtained using the control materials provided by the manufacturer. In reference subjects, the 2.5-97.5th percentiles were found to be 4.52-22.33 and 4.84-21.88mg/L for \u3baFLC and \u3bbFLC, respectively. The range for \u3ba/\u3bb ratio (0.65-2.36) was validated with the values obtained from subjects with polyclonal hypergammaglobulinemia. In retesting 15 samples from blood donor subjects with a different lot of reagents, mean bias percentages of 17.60 for \u3baFLC and 15.26 for \u3bbFLC were obtained. CONCLUSIONS: These findings confirm the lot-to-lot variability of the FLC assays also in the measurement of polyclonal light chains, as well as the need to carefully validate the reference value