Biological variation studies define the physiological fluctuation of analyte concentrations in a biological fluid around its homeostatic set point . Knowledge of the biological variation of FLCs in serum is useful when interpreting monitoring data for individual patients. Braga et al.  studied the biological variation of sFLC measurements in 21 healthy volunteers (12 women and 9 men), measured at the same time on the same day, every 2 weeks over the course of 2 months. λ sFLC concentrations were significantly higher in men than women (p<0.01), whereas no difference was found for κ sFLC concentrations. Intra-individual variances of κ or λ FLCs were similar (8.1% and 7.0%, respectively), and were not different between men and women. By contrast, the inter-individual variance of λ sFLCs was higher than that of κ sFLCs (27.5% vs. 14.1%, respectively), and was higher for men than women (33.0% vs. 22.6%, respectively). The reference change value (RCV) defines the minimum significant difference (p<0.05) between two consecutive measurements in the same individual. In this study the RCV for κ and λ sFLCs was similar: 22.6% and 19.6%, respectively. Similar findings were reported by Hansen et al. .
Katzmann et al.  studied the long-term biological variation of monoclonal FLCs in 158 patients with clinically stable monoclonal gammopathy. For each patient, at least three serial samples were obtained within a 5 year period. During the study, each patient received no treatment, had no change in clinical diagnosis, and had a <5 g/L change in serum monoclonal immunoglobulin quantification by protein electrophoresis. A total of 52/158 patients had measurable monoclonal sFLCs (defined as iFLC ≥100 mg/L with an abnormal κ/λ sFLC ratio). The total coefficient of variation (CV) for iFLC measurements was 28.4%, which was almost entirely attributable to biological variation (CV=27.8%) and, to a lesser extent, due to inter-assay analytical variation (CV=5.8%). The variation in iFLC was more comparable to that of monoclonal protein quantification by urine protein electrophoresis (Total CV=35.8%) than serum protein electrophoresis (Total CV=8.1%). This is likely to reflect the short serum half-life of FLCs compared with intact immunoglobulins (Chapter 3). The RCV for monoclonal sFLCs was 54.5%. This value is significantly higher than that reported by other smaller studies  and may reflect differences in the length of patient follow-up (5 years vs. less than a week). Several authors now recommend that biological variation data should be taken into account to update the definitions of sFLC response criteria.