Accuracy of determination of free light chains (Kappa and Lambda) in plasma and serum by Swedish laboratories as monitored by external quality assessment

Background: Free light chain (FLC) measurements are important in diagnosing monoclonal gammopathies. As FLC are heterogeneous, different reagents and instruments for measuring FLC concentrations may give diverging results that affect assessment of patients with monoclonal gammopathies. Here we investigated agreement be-tween different FLC methods using data from the Swedish external quality assurance (EQA) programme.Methods: The two main FLC assays, N Latex FLC (Siemens) and Serum Freelite (The Binding Site), using four nephelometric or turbidimetric instrument platforms, were compared. Results from 27 EQA rounds distributed to 11-16 Swedish hospital laboratories during 2015-2020 were investigated.Results: The kappa (Kappa) FLC measurements deviated significantly over time, but when only nephelometry was used, deviation from the mean was lower (median ranges:-5% to 13 %). The CV was significantly higher for the Freelite assay (mean CV = 8.7) than for the N latex assay (mean CV = 5.7) (p < 0.0001). The coefficient of determination between all combinations of reagents and instrument platforms used was generally good (r2 = 0.76-0.87), and the correlation slope acceptable (0.81-1.2). For lambda (lambda) FLC measurements, no concordance between combinations of instruments and reagents is apparent, deviating between-40 % to + 48 % from the mean. The CV was significantly higher for the combination with nephelometry and the Freelite assay (CV mean = 13.9 %) than nephelometry and the N latex assay (CV mean = 9.9 %) (p <0.001). The coefficient of deter-mination varied between combinations of reagents and instrument platforms (r2 = 0.59-0.89) and the slope ranged between 0.48 and 1.5. Significant differences between the two reagents used were sometimes noted.Conclusions: Imprecision in lambda FLC affects the Kappa FLC/lambda FLC ratio. This may be important in clinical assessment of patients, especially differentiating between monoclonal and polyclonal gammopathies.