title: Serum free light chain reference values: a critical approach.
abstract: OBJECTIVE
  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.
  
  
  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 κ/λ 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 κFLC and of 16.72% for λFLC. 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 κFLC and λFLC, respectively. The range for κ/λ 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 κFLC and 15.26 for λFLC 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 values.
authors: Department of Laboratory Medicine, University-Hospital of Padova, Italy. sara.altinier@sanita.padova.it
authors: Sara
authors: S
authors: Altinier
authors: Mara
authors: M
authors: Seguso
authors: Martina
authors: M
authors: Zaninotto
authors: Mariacristina
authors: M
authors: Varagnolo
authors: Fausto
authors: F
authors: Adami
authors: Paolo
authors: P
authors: Angeli
authors: Mario
authors: M
authors: Plebani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry / Q000592:standards; D010265:Paraproteinemias; D012015:Reference Standards; D012016:Reference Values; D015203:Reproducibility of Results
chemical_list: D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains