Performance Evaluation of Serum Free Light Chain Analysis

Messiaen, Anne-Sophie; Sloovere, Maxime M W De; Claus, Paul-Emile; Vercammen, Martine; Hoovels, Lieve Van; Heylen, Olivier; Debrabandere, Johan; Vanpoucke, Hilde; Smet, Dieter De

doi:10.1093/ajcp/aqx037

Cited by 25 publications

(9 citation statements)

References 24 publications

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“…The technical and analytical characteristics of the N-Latex FLC and Freelite assays have been thoughtfully described elsewhere ( 7 - 10 ). Previous evidence has shown that numerical values produced by the two different systems can have remarkable differences and this aspect has also been evidenced in our study, where higher concentrations are paralleled by an increase in absolute differences ( 11 , 12 ). Several causes can be preferred for explaining inter-assay variability.…”

Section: Discussionsupporting

confidence: 87%

“…First, the Freelite method uses polyclonal Ab, whilst the N-Latex is based on a cocktail of monoclonal Ab. It is hence conceivable that less antigenic determinants may be better recognized by the N-Latex assay, whereas some FLC abnormally expressed in plasma cell dyscrasia could escape detection ( 2 , 11 , 12 ). Previous data underpins that the discrepancies observed between the two methods may be attributable to polymerization of FLC, leading to potential overestimation using the Freelite method, with concurrent underestimation using the N-Latex assay due to binding sites masking ( 13 , 14 ).…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Freelite and N-Latex serum free light chain assays

Daves

Piccin

Roccaforte

et al. 2021

Biochem. med. (Online)

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Introduction The measurement of serum free light chain (FLC) represents a fundamental aspect on the assessment of patients with monoclonal gammopathies (MG). Different analytical methods for FLC have become available with the possibility to obtain different value with a substantial impact on the assessment of patients with MG. This study aimed to evaluate FLC results obtained with two different assays and how the difference value obtained can impact in the patient’s assessment. Materials and methods Ninety-three patient serum samples that underwent analysis for FLC with two different methods, Serum Freelite (The Binding Site, Birmingham, UK) and N-Latex FLC (Siemens, Marburg, Germany), were included in this retrospective study. Statistical analysis was performed to evaluate correlation, difference, and the grade of concordance between the results obtained with the two methods. Results Significant statistical differences between the results obtained from the two methods were found (P < 0.05). A good correlation was found (0.99 for κ FLC, 0.95 for λ FLC, and 0.94 for the κ/λ ratio, respectively). We found a weighted kappa value of 0.65 for κ/λ ratio, 0.65 for λ FLC and 0.90 for κ FLC. A positive bias found with the Bland-Altman plot mirrors overestimation of κ FLC and κ/λ ratio with Freelite compared to N-Latex, whilst a negative bias underscores underestimation of λ FLC by Freelite compared to N-Latex. Conclusion Although in general the concordance between Freelite and N-Latex appears satisfactory, several discrepancies could be evidenced and consequently the two assays are not interchangeable.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Comparison of Freelite and N-Latex serum free light chain assays

Daves

Piccin

Roccaforte

et al. 2021

Biochem. med. (Online)

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“…Messiaen AS et al . documented a lower correlation coefficient for FLC lambda (0.93) than FLC kappa (0.98) results in comparison of monoclonal and polyclonal reagent on the same analyser ( 19 ). Our results demonstrate that occasionally progressive disease would not be recognized in certain patients using one of the applied analysers.…”

Section: Discussionmentioning

confidence: 97%

“…Numerous studies present evaluation results of FLCs test. Most of them involve evaluation of polyclonal reagent on different not reagent-optimized analytical platforms for FLCs tests ( 19 , 22 ). This evaluation study is conducted on reagent-optimized analysers.…”

Section: Discussionmentioning

confidence: 99%

Verification study of free light chains assays on reagent-optimized analysers

Šegulja

Matišić

Barišić

et al. 2019

Biochem. med. (Online)

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Introduction: Our aim was to compare analytical specifications of two assays (monoclonal vs. polyclonal) for free light chains (FLCs) quantification optimized for two different analytical platforms, nephelometer ProSpec (Siemens, Erlangen, Germany) and turbidimetric analyser Optilite (The Binding Site, Birmingham, UK). Materials and methods: The evaluation included verification of the precision, repeatability and reproducibility, estimation of accuracy and method comparison study with 37 serum samples of haematological patients. Kappa and lambda FLC were measured in each sample by both methods and kappa/lambda ratio was calculated. Results: Results show satisfactory precision of both methods with coefficients of variation for ProSpec of CVwr = 2.20% and CVbr = 3.44%, and for Optilite CVwr = 2.82% and CVbr = 4.15%. Estimated bias for FLC lambda was higher on the ProSpec analyser, but bias for FLC kappa was higher on the Optilite analyser. Correlation coefficients were 0.98; P < 0.001 for FLC kappa and 0.97; P < 0.001 for FLC lambda. Considering normal/pathological FLC ratio moderate agreement within assays was detected (κ = 0.621). When the results were categorized according to criteria for progressive disease, 4/37 (0.10) cases were differently classified. Lambda FLC values by Optilite in three samples with monoclonal FLC lambda were more than twelve times higher than by ProSpec. A 25% difference in FLC ratio was detected in 16/37 (0.43) and 50% difference in 13/37 (0.35) patients. Conclusions: All manufacturers’ precision claims could not be achieved in the verification study. The comparison of results to biological variations data showed that coefficients of variations are acceptable for both assays. The assays should not be used interchangeably in haematological patients.

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“…Most of the tests measure the presence of the soluble immune complexes by detecting the changes in turbidity through nephelometric or turbidimetric methods. These methods can suffer from high imprecision at low concentrations, nonlinear immunoreactivity on dilutions, and/or the inability to detect antigen excess, leading to underestimation of mFLC concentration [14–17], all of which can potentially impact the κ/λ ratio. Freelite from The Binding Site was the first available method in 2001 and has been developed as six independent tests adapted to different nephelometry and turbidimetry analyzers.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a new ELISA assay for monoclonal free‐light chain detection in patients with cardiac amyloidosis

Abroud¹,

Beldi‐Ferchiou

Audard³

et al. 2022

eJHaem

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The causal protein of amyloid light-chain (AL) amyloidosis is a monoclonal immunoglobulin free light chain (mFLC), which must be quantified in the serum for patient diagnosis and monitoring. Several manufacturers commercialize immunoassays that quantify total kappa (κ) and lambda (λ) FLC, but results can differ greatly between these tests. Here, we compared a recently developed enzyme-linked immunosorbent assay (ELISA) (Sebia) with N-Latex immunonephelometry (Siemens) in 96 patients diagnosed with AL amyloidosis (histologically confirmed) and 48 non-AL patients sent to our referral center for suspicion of cardiac amyloidosis. ELISA free-light chain difference (dFLC) were lower than N-Latex values, and agreement between methods was reduced in the case of involved λ FLC. Diagnosis sensitivity and specificity were >85% with both assays. A receiver operating characteristic analysis indicated that ELISA performances could be improved by using a higher value for the lower limit of the κ/λ ratio. We also assessed Freelite (The Binding Site) in a subgroup of these same AL patients, including 18 cases with normal κ/λ ratio by at least one assay. Only two patients had normal κ/λ ratio with all three assays. Overall, ELISA demonstrated slightly lower sensitivity than N-Latex but may be an alternative to nephelometry/turbidimetry in certain difficult cases.

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Performance Evaluation of Serum Free Light Chain Analysis

Abstract: FLC analysis requires continuous awareness of analytical limitations. Monitoring of disease response requires FLC analysis on the same platform using the same reagents.

Cited by 25 publications

References 24 publications

Comparison of Freelite and N-Latex serum free light chain assays

Comparison of Freelite and N-Latex serum free light chain assays

Verification study of free light chains assays on reagent-optimized analysers

Evaluation of a new ELISA assay for monoclonal free‐light chain detection in patients with cardiac amyloidosis

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