Establishment and validation of serum free light chain reference intervals in an ethnic Chinese population.

Background: Quantification of serum free light chains (FLC) and calculation of a kappa/lambda ratio using polyclonal antisera based immunoassays provide laboratories with a sensitive alternative to urine protein electrophoresis (UPE). However, the published 0.26 - 1.65 serum FLC kappa/lambda ratio reference intervals may not be suitable for different ethnic populations (such as the Han Chinese population presented) and require validation. This is particularly important where there are significant differences in ethnicity, and hence HLA prevalence, in the population studied. Methods: Serum FLC reference intervals were determined using 326 Han Chinese blood donor volunteers. Sensitivities and specificities for the (i) serum FLC kappa/lambda ratio reference interval and (ii) UPE analyses were determined using 68 pre-treatment, serum immunofixation (sIFE) positive multiple myeloma (MM) patient samples, 54 sera from MM patients undergoing treatment, and 56 sIFE-negative samples from patients with no plasma cell dyscrasia (PCD). Results: The 100% range for the serum FLC kappa/lambda ratio in this Han Chinese population was 0.32 - 1.52. Both Han Chinese blood donors and published kappa/lambda ratio reference ranges demonstrated higher diagnostic sensitivity and specificity for PCD than was seen with UPE. Highly abnormal serum FLC kappa/lambda ratios were observed in 68% of MM patients who had a negative UPE. Furthermore, a MM screening panel of SPE plus serum FLC assays achieved 100% diagnostic sensitivity compared to 97% for a UPE plus SPE algorithm. For MM patients undergoing therapy, 70% of UPE negative samples displayed an abnormal FLC ratio. Conclusions: This study confirms the requirement to verify normal FLC reference ranges in local populations. This Han Chinese reference range is narrower than the published range. FLC testing provides a robust, sensitive, and specific alternative to classic UPE assessment.