Serum Free Light Chain Assay: Shift Toward a Higher κ/λ Ratio

Serum free light chain (FLC) assays are essential in diagnosing plasma cell disorders. Prior research has shown that FLC κ and λ ratios serve as diagnostic markers. However, discrepancies in assay performance remain unresolved. No prior work had resolved how different assays affect κ/λ ratios in clinical settings. This gap motivated a comparison of monoclonal and polyclonal FLC assays. That uncertainty drove the need to assess assay variability and renal impact. It was already known that renal function influences FLC clearance. No prior work had resolved the extent of bias between Freelite and N Latex methods. This gap motivated the current investigation into diagnostic consistency.

The study aimed to compare monoclonal and polyclonal FLC κ and λ assays in clinical use. The specific problem addressed was the variability in κ/λ ratio results across different methods. The motivation stemmed from observed diagnostic inconsistencies in clinical practice. No prior work had resolved the impact of renal function on assay outcomes. This study sought to evaluate Freelite and N Latex assays in a single center. The goal was to determine if one method offers better specificity for FLC diagnostics. That uncertainty drove the need to assess bias and correlation between assays. This should be considered when interpreting FLC κ and λ results.

The study compared Freelite and N Latex assays on the BN ProSpec System. Serum FLCs were analyzed from 102 patients in a single academic center. Protein electrophoresis and immunofixation data were collected for comparison. C-reactive protein and eGFR measurements were also included in the analysis. Imprecision and inaccuracy were evaluated using standard statistical metrics. Kendall τ correlation coefficients were calculated to assess agreement between methods. Renal function was estimated using eGFR to evaluate assay interference. Both methods showed acceptable performance metrics but poor correlation.

Method evaluation showed acceptable imprecision (<4.4%) and inaccuracy (<12.9%). Freelite and N Latex assays showed poor agreement with constant and proportional bias. The Freelite assay was affected by renal impairment estimated via eGFR. N Latex κ/λ ratios remained stable regardless of renal function. Freelite κ/λ ratios in 98% of controls exceeded standard diagnostic ranges. Retrospective data from 2011 to 2017 showed a shift toward higher κ/λ ratios. Freelite results showed a median shift compared to N Latex. This shift may impair diagnostic specificity for borderline κ/λ increases.

The Freelite assay is influenced by renal function, unlike the N Latex method. A shift toward higher κ/λ ratios was observed in Freelite results over time. This shift may reduce diagnostic specificity for borderline κ/λ increases. The N Latex assay appears less affected by renal impairment. Both methods showed acceptable performance metrics but poor correlation. This should be considered when interpreting FLC κ and λ results. The authors propose that assay variability affects diagnostic interpretation. No prior work had resolved the extent of bias between Freelite and N Latex methods.