Detection of serum free light chains: the problem with antigen excess

Bosmann, Markus; Kössler, Jürgen; Stolz, H. N. P.; Walter, Ulrich; Knop, Stefan; Steigerwald, Udo

doi:10.1515/cclm.2010.283

Cited by 31 publications

(26 citation statements)

References 14 publications

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“…Non-linearity, defined as a more than 2-fold but less than 4-fold difference between the results obtained at the 2000-fold and 100-fold dilution, was found in 6% of the samples for κ FLC and in 0.5% of the samples for λ FLC [8]. These numbers surpassed the estimates of two earlier reports [9,10] but were later confirmed in a retrospective analysis (also on BNII) showing antigen excess in 5% to 8% of the samples for κ FLC and in 1.5% to 4.5% of the samples for λ FLC [11]. In the latter study, nonlinearity was detected in 5% to 6.9% of the samples for κ FLC and in 2% to 4.2% of the samples for λ FLC [11].…”

Section: Introductioncontrasting

confidence: 44%

“…In our January 2008 to February 2010 series, we found 5.4% antigen excess for κ FLC and 3.1% for λ FLC in 2088 consecutive samples [8]. Our incidence outnumbered the 2.2% for κ and λ FLC combined (100-fold and 2000-fold dilution) of Bosmann et al [9] and the 0.12% for κ FLC (100-fold and 400-fold dilution) of Murata et al [10] on the BNII platform. We continued to follow the incidence of antigen excess in subsequent patient series and aimed to find the reason for the differences.…”

Section: Discussionmentioning

confidence: 46%

See 1 more Smart Citation

Overestimation of free light chain antigen excess rate

Vercammen

Broodtaerts

Meirlaen

et al. 2015

Clinica Chimica Acta

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Section: Introductioncontrasting

confidence: 44%

Section: Discussionmentioning

confidence: 46%

Overestimation of free light chain antigen excess rate

Vercammen

Broodtaerts

Meirlaen

et al. 2015

Clinica Chimica Acta

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“…Little discussion of analytical platform-related measurement variability has occurred. Several papers and reviews (including guidance from the manufacturer) have highlighted the potential for non-linear behaviour and the necessity to identify samples which demonstrate antigen or antibody excess [3][4][5][6][7][8][9]14]. It is likely that this will be very different in a population screening exercise compared to use in a tertiary centre with a high pretest prevalence.…”

Section: Discussionmentioning

confidence: 99%

Defining the impact of individual sample variability on routine immunoassay of serum free light chains (sFLC) in multiple myeloma

Murng

Follows

Whitfield

et al. 2013

Clinical and Experimental Immunology

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SummarySerum free light chain (sFLC) measurement has gained widespread acceptance and is incorporated into various diagnostic and response criteria. Nonlinearity and antigen excess are the main causes of 'variability' in the measurement of sFLC using immunoassay, but the impact of these on measurement has been unclear. We performed a retrospective evaluation using a dilutional strategy to detect these phenomena. A total of 464 samples in 2009 and 373 samples in 2010 were analysed for sFLC. Non-linearity was detected in both high and apparently normal sFLC. Major non-linearity of more than twofold is common in high kappa (20·2%) and lambda (14·1%). It is less common in samples with apparently normal levels -kappa (6·4%) and lambda (9·5%). 9·4% of kappa and 15·5% of lambda showed antigen excess at screening dilutions. 34·4% of the samples had either non-linearity or antigen excess. We conclude that significant measurement variability is common in the measurement of sFLC. There is currently no reliable technique to detect non-linearity phenomena unless a serial dilution strategy is applied to every analysis. We recommend that laboratories routinely reporting sFLC results for clinical services need appropriate strategies for addressing these issues. Clinicians should be aware of these limitations in interpretation of sFLC assay for individual patients. Future guidelines should adopt action thresholds which are grounded firmly in test performance parameters.

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“…However, despite the usefulness of this method, several analytical problems have continuously been faced, including lot-to-lot variability of reagents, antigen excess, unrecognizable epitopes, and excessive polymerization [5–8]. The Freelite assay has the limitations of poor postdilution linearity and relative imprecision, as well as increased likelihood of showing false negative results due to antigen excess in patients with extremely high FLC concentration [3, 7]. To overcome these problems, a new N Latex assay (Siemens Healthcare Diagnostics GmbH, Marburg, Germany) using monoclonal antibodies has been developed and recently made available [9].…”

Section: Introductionmentioning

confidence: 99%

Clinical Comparisons of Two Free Light Chain Assays to Immunofixation Electrophoresis for Detecting Monoclonal Gammopathy

Kim

Shin

et al. 2014

BioMed Research International

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Free light chains (FLCs) are useful biomarkers for the diagnosis and monitoring of various plasma cell dyscrasias. One hundred fifty-seven samples from 120 patients for screening or monitoring of monoclonal gammopathy (MG) were included. The new N Latex FLC assays (Siemens Healthcare Diagnostics GmbH, Germany) were compared with the Freelite FLC assays (The Binding Site Ltd., UK) and the results were analyzed with those of immunofixation electrophoresis (IFE). The Freelite FLC assay showed significantly wider assay ranges than the N Latex FLC assay. The correlation coefficients of the two FLC kappa (κ) assays, lambda (λ) assays, and the κ/λ ratio were 0.9792, 0.8264, and 0.9064, respectively. The concordance rate was 84.7% for the FLC κ assays, 79.6% for FLC λ, and 89.2% for the κ/λ ratio. The clinical sensitivity and specificity of the κ/λ ratios were 72.2% and 93.6% for the Freelite assay and 64.6% and 100% for the N Latex FLC assay. Two FLC assays showed good correlations and concordance. However, the clinical sensitivity of the κ/λ ratio was higher in the Freelite FLC assays; clinical specificity was higher in the N Latex FLC assay. Both FLC assays seem to have limited clinical utility in detecting MG in certain clinical settings.

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Detection of serum free light chains: the problem with antigen excess

Cited by 31 publications

References 14 publications

Overestimation of free light chain antigen excess rate

Overestimation of free light chain antigen excess rate

Defining the impact of individual sample variability on routine immunoassay of serum free light chains (sFLC) in multiple myeloma

Clinical Comparisons of Two Free Light Chain Assays to Immunofixation Electrophoresis for Detecting Monoclonal Gammopathy

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