Ercan, M.Fırat Oğuz, E.Özcan, M.Alp, H.H.2025-09-032025-09-0320260009-898110.1016/j.cca.2025.1205452-s2.0-105012832739https://doi.org/10.1016/j.cca.2025.120545https://hdl.handle.net/20.500.14720/28403Serum light immunoglobulin chains (LCs) are critical biomarkers for the diagnosis, prognosis, and treatment response monitoring in monoclonal plasma cell dyscrasias. Robust performance standards based on biological variation (BV) data are essential for optimizing patient care. This study aimed to provide updated BV estimates for serum free LCs (κ and λ) as well as their κ/λ LC ratio. Serum samples from 25 healthy volunteers (10 men, 15 women) were collected weekly over approximately 9 weeks. Serum free LCs were measured in duplicate using the Roche Cobas c501 analyzer. BV estimates with 95 % confidence intervals were calculated using coefficient of variation (CV) in ANOVA for the entire group and by sex, following assessments for outliers, normality, steady-state conditions, and variance homogeneity. The within-subject BV (CVI) estimates were 9.2 %, 8.6 %, 6.6 % for free κ, free λ, free κ/λ ratio, respectively. The between-subject BV (CVG) estimates were 24.6 %, 26.6 %, and 17.5 %for free κ, free λ and free κ/λ ratio, respectively. No significant sex differences were observed for CVI with the exception of free κ and free κ/λ ratio or CVG in serum free LCs and their ratio. Free LCs and their κ/λ ratio exhibited marked individuality. Analytical performance specifications (APSs) for desirable imprecision and bias ranged 3.9 %–5.4 %, 4.3 %–5.8 % and 2.9 %–4.6 % for free κ, free λ and free κ/ λ ratio, respectively. This study provides updated, well-characterized BV estimates for serum free (κ and λ) and free κ/λ ratio, providing essential data to define APSs. The individuality of κ and λ underscores the importance of prioritizing reference change values over traditional reference intervals for improved diagnosis and monitoring in clinical practice. © 2025eninfo:eu-repo/semantics/closedAccessAnalytical Performance SpecificationsBiological VariationSerum Free Light Immunoglobulin ChainsArticle578Q2Q1