Within-and Between-Subject Biological Variation Estimates of Serum Free Light Immunoglobulin Chains in Healthy Individuals in Turkey

Abstract

Serum 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 (kappa and lambda) as well as their kappa/lambda 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, steadystate conditions, and variance homogeneity. The within-subject BV (CVI) estimates were 9.2 %, 8.6 %, 6.6 % for free kappa, free lambda, free kappa/lambda ratio, respectively. The between-subject BV (CVG) estimates were 24.6 %, 26.6 %, and 17.5 %for free kappa, free lambda and free kappa/lambda ratio, respectively. No significant sex differences were observed for CVI with the exception of free kappa and free kappa/lambda ratio or CVG in serum free LCs and their ratio. Free LCs and their kappa/lambda 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 kappa, free lambda and free kappa/ lambda ratio, respectively. This study provides updated, well-characterized BV estimates for serum free (kappa and lambda) and free kappa/lambda ratio, providing essential data to define APSs. The individuality of kappa and lambda underscores the importance of prioritizing reference change values over traditional reference intervals for improved diagnosis and monitoring in clinical practice.