Biologic variation of immunoglobulin free light chains in serum

The measurement of serum kappa and lambda free light chains (FLC) and kappa/lambda FLC ratio calculation are recommended for screening, prognostic evaluation and monitoring of multiple myeloma and related plasma cell disorders. Given the lack of reliable data available in literature, in this study we assessed biologic variability components of FLCs and FLC ratio by an accurately designed protocol. We collected five blood specimens from each of 21 healthy volunteers (9 men and 12 women; age range, 23-54 years) on the same day, every two weeks for two months. Serum specimens were stored at -80 degrees C until analysis and analyzed in a single run in duplicate using a SPAPLuS immunoturbidimetric platform and Freelite reagents (The Binding Site). Data were analyzed by ANOVA. Serum lambda FLC concentrations were significantly (P < 0.01) higher in men. The inter-individual variance of lambda FLC was higher than that of kappa FLC. Within-and between-subject CVs were 8.1% and 14.1% for kappa FLC, 7.0% and 27.5% for lambda FLC, and 4.5% and 15.3% for FLC ratio. All parameters had marked individuality showing that the use of population-based reference intervals could be inadequate for test interpretation. The reference change value was between 20% and 30% depending from the assay imprecision. Desirable analytical goals for imprecision (CV), bias and total error were < 4.0%, +/- 4.1% and +/- 10.7% for FLC, < 3.5%, +/- 7.1% and +/- 12 .9% for lambda FLC, and < 2.3%, +/- 4.0% and +/- 7.7% for FLC ratio.