Clinical implication by differential analytical performances of serum free light chain quantitation analysis using fully automated analyzers
-
Shin Young Yun
,
John Hoon Rim
,
Hak Park
Abstract
Objectives
Free light chain (FLC) is used for the diagnosis and prediction with regard to the progression risk of plasma cell disorders and Freelite reagent using the SPAplus analyzer (The Binding Site) has been one of the widely used option. However, N Latex FLC reagent with the Atellica CH 930 analyzer (Siemens Healthineers) has shown the advantages of automation and high throughput. We aimed to evaluated clinical implication by differential analytical performances of two assays.
Methods
A total of 322 serum samples were collected from 193 patients requested for FLC analysis including 131 multiple myeloma patients. The precision, linearity, dilution recovery of N Latex FLC assay was evaluated. We compared the two assays and analyzed the monomer-dimer pattern for discrepant results.
Results
The precision, linearity, and dilution recovery performance was appropriate for the routine use in clinical laboratories. Despite the good correlation within normal range, proportional bias up-to 170% was observed in samples with high concentrations especially for lambda. The higher value samples with N Latex FLC assay contained more monomer forms than controls. All opposite changes of FLC burden by the N Latex FLC assay proved to present concordant dynamic changes when assessed by serum protein electrophoresis.
Conclusions
Clinical laboratories should be aware of the inter-assay variability of FLC quantitative measurements using different platforms, especially for high concentrations of both kappa and lambda measurements, possibly due to monomer/dimer ratio diversity. Clinical interpretations for multiple myeloma disease status might not be dramatically affected only when the same assay is utilized during follow-up periods.
Funding source: Siemens Healthineers
-
Research funding: This study was supported by research funding from Siemens Healthineers.
-
Author contributions: S.Y.Y. and J.H.R. were responsible for acquiring data, analysing data, interpreting results and drafted the manuscript. H.P., H.K., S.G.L and J.B.L. supervised the experiment, interpreted data and revised manuscript. S.Y.Y, J.H.R., H.P., H.K., S.G.L and J.B.L all approved the final version.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: All samples were collected using a well-defined protocol with approval from the Institutional Review Board of Severance Hospital (IRB No. 4-2020-1041 and 4-2022-1443).
-
Data availability: The datasets analysed during the current study are available from the corresponding author on reasonable request.
References
1. Köhler, G. Immunoglobulin chain loss in hybridoma lines. Proc Natl Acad Sci U S A 1980;77:2197–9. https://doi.org/10.1073/pnas.77.4.2197.Suche in Google Scholar PubMed PubMed Central
2. Solomon, A. Light chains of human immunoglobulins. Methods Enzymol 1985;116:101–21. https://doi.org/10.1016/s0076-6879(85)16008-8.Suche in Google Scholar PubMed
3. Leitzgen, K, Knittler, MR, Haas, IG. Assembly of immunoglobulin light chains as a prerequisite for secretion. A model for oligomerization-dependent subunit folding. J Biol Chem 1997;272:3117–23. https://doi.org/10.1074/jbc.272.5.3117.Suche in Google Scholar PubMed
4. Rajkumar, SV, Dimopoulos, MA, Palumbo, A, Blade, J, Merlini, G, Mateos, MV, et al.. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538–48. https://doi.org/10.1016/s1470-2045(14)70442-5.Suche in Google Scholar PubMed
5. Rajkumar, SV, Kyle, RA, Therneau, TM, Melton, LJ3rd, Bradwell, AR, Clark, RJ, et al.. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005;106:812–7. https://doi.org/10.1182/blood-2005-03-1038.Suche in Google Scholar PubMed PubMed Central
6. Dispenzieri, A, Kyle, RA, Katzmann, JA, Therneau, TM, Larson, D, Benson, J, et al.. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008;111:785–9. https://doi.org/10.1182/blood-2007-08-108357.Suche in Google Scholar PubMed PubMed Central
7. Kastritis, E, Terpos, E, Moulopoulos, L, Spyropoulou-Vlachou, M, Kanellias, N, Eleftherakis-Papaiakovou, E, et al.. Extensive bone marrow infiltration and abnormal free light chain ratio identifies patients with asymptomatic myeloma at high risk for progression to symptomatic disease. Leukemia 2013;27:947–53. https://doi.org/10.1038/leu.2012.309.Suche in Google Scholar PubMed
8. Cherry, BM, Korde, N, Kwok, M, Manasanch, EE, Bhutani, M, Mulquin, M, et al.. Modeling progression risk for smoldering multiple myeloma: results from a prospective clinical study. Leuk Lymphoma 2013;54:2215–8. https://doi.org/10.3109/10428194.2013.764419.Suche in Google Scholar PubMed PubMed Central
9. Kyrtsonis, MC, Vassilakopoulos, TP, Kafasi, N, Sachanas, S, Tzenou, T, Papadogiannis, A, et al.. Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. Br J Haematol 2007;137:240–3. https://doi.org/10.1111/j.1365-2141.2007.06561.x.Suche in Google Scholar PubMed
10. Snozek, CL, Katzmann, JA, Kyle, RA, Dispenzieri, A, Larson, DR, Therneau, TM, et al.. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 2008;22:1933–7. https://doi.org/10.1038/leu.2008.171.Suche in Google Scholar PubMed PubMed Central
11. Dingli, D, Kyle, RA, Rajkumar, SV, Nowakowski, GS, Larson, DR, Bida, JP, et al.. Immunoglobulin free light chains and solitary plasmacytoma of bone. Blood 2006;108:1979–83. https://doi.org/10.1182/blood-2006-04-015784.Suche in Google Scholar PubMed PubMed Central
12. Larsen, JT, Kumar, SK, Dispenzieri, A, Kyle, RA, Katzmann, JA, Rajkumar, SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia 2013;27:941–6. https://doi.org/10.1038/leu.2012.296.Suche in Google Scholar PubMed PubMed Central
13. Claveau, JS, Savary Bélanger, S, Ahmad, I, Delisle, JS, De Guire, V, Roy, J, et al.. Early free light chain reduction following treatment initiation predicts favorable outcome in intact immunoglobulin myeloma. Blood Cancer J 2022;12:3. https://doi.org/10.1038/s41408-021-00600-6.Suche in Google Scholar PubMed PubMed Central
14. Hasib Sidiqi, M, Gertz, MA. Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021. Blood Cancer J 2021;11:90. https://doi.org/10.1038/s41408-021-00483-7.Suche in Google Scholar PubMed PubMed Central
15. Bossuyt, X, Delforge, M, Reynders, M, Dillaerts, D, Sprangers, B, Fostier, K, et al.. Diagnostic thresholds for free light chains in multiple myeloma depend on the assay used. Leukemia 2018;32:1815–8. https://doi.org/10.1038/s41375-018-0041-0.Suche in Google Scholar PubMed
16. Fleming, CKA, Swarttouw, T, de Kat Angelino, CM, Jacobs, JFM, Russcher, H. Method comparison of four clinically available assays for serum free light chain analysis. Clin Chem Lab Med 2019;58:85–94. https://doi.org/10.1515/cclm-2019-0533.Suche in Google Scholar PubMed
17. Caponi, L, Romiti, N, Koni, E, Fiore, AD, Paolicchi, A, Franzini, M. Inter-assay variability in automated serum free light chain assays and their use in the clinical laboratory. Crit Rev Clin Lab Sci 2020;57:73–85. https://doi.org/10.1080/10408363.2019.1670133.Suche in Google Scholar PubMed
18. Kaplan, B, Golderman, S, Aizenbud, B, Esev, K, Kukuy, O, Leiba, M, et al.. Immunoglobulin-free light chain monomer-dimer patterns help to distinguish malignant from premalignant monoclonal gammopathies: a pilot study. Am J Hematol 2014;89:882–8. https://doi.org/10.1002/ajh.23773.Suche in Google Scholar PubMed
19. Caponi, L, Franzini, M, Koni, E, Masotti, S, Petrini, M, Paolicchi, A. Discrepancy between FLC assays: only a problem of quantification? Clin Chem Lab Med 2016;54:1111–3. https://doi.org/10.1515/cclm-2015-1262.Suche in Google Scholar PubMed
20. Gatt, ME, Kaplan, B, Yogev, D, Slyusarevsky, E, Pogrebijski, G, Golderman, S, et al.. The use of serum free light chain dimerization patterns assist in the diagnosis of AL amyloidosis. Br J Haematol 2018;182:86–92. https://doi.org/10.1111/bjh.15387.Suche in Google Scholar PubMed
21. Caponi, L, Koni, E, Romiti, N, Paolicchi, A, Franzini, M. Different immunoreactivity of monomers and dimers makes automated free light chains assays not equivalent. Clin Chem Lab Med 2018;57:221–9. https://doi.org/10.1515/cclm-2018-0412.Suche in Google Scholar PubMed
22. CLSI. Evaluation of precision of quantitative measurement procedures; approved guideline, 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.Suche in Google Scholar
23. CLSI. Evaluation of linearity of quantitative measurement procedures, 2nd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2020.Suche in Google Scholar
24. CLSI. Measurement procedure comparison and bias estimation using patient samples, 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.Suche in Google Scholar
25. Yang, Y, Han, X, Zheng, G, Cai, Z. Comparison of two serum free light chain assays for the diagnosis of primary plasma cell malignant proliferative disease. Health Sci Rep 2019;2:e113. https://doi.org/10.1002/hsr2.113.Suche in Google Scholar PubMed PubMed Central
26. Schieferdecker, A, Hörber, S, Ums, M, Besemer, B, Bokemeyer, C, Peter, A, et al.. Comparison of three different serum-free light-chain assays-implications on diagnostic and therapeutic monitoring of multiple myeloma. Blood Cancer J 2020;10:2. https://doi.org/10.1038/s41408-019-0267-8.Suche in Google Scholar PubMed PubMed Central
27. Daves, M, Piccin, A, Roccaforte, V, Lippi, G. Comparison of Freelite and N-Latex serum free light chain assays: a critical review. Biochem Med 2021;31:030701. https://doi.org/10.11613/bm.2021.030701.Suche in Google Scholar PubMed PubMed Central
28. Tate, JR, Hawley, C, Mollee, P. Response to article by Caponi et al. about serum free light chains. Clin Chem Lab Med 2018;57:e1–e2. https://doi.org/10.1515/cclm-2018-0994.Suche in Google Scholar PubMed
29. Sprangers, B, Claes, K, Evenepoel, P, Kuypers, D, Poesen, K, Delforge, M, et al.. Comparison of 2 serum-free light-chain assays in CKD patients. Kidney Int Rep 2020;5:627–31. https://doi.org/10.1016/j.ekir.2020.01.019.Suche in Google Scholar PubMed PubMed Central
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0050).
© 2023 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- ChatGPT: Angel or Demond? Critical thinking is still needed
- Mini Review
- Diagnostic accuracy of Siemens SARS-CoV-2 Antigen (CoV2Ag) chemiluminescent immunoassay for diagnosing acute SARS-CoV-2 infection: a pooled analysis
- Opinion Papers
- Neurofilament light chain as neuronal injury marker – what is needed to facilitate implementation in clinical laboratory practice?
- Clinical evidence requirements according to the IVDR 2017/746: practical tools and references for underpinning clinical evidence of IVD-MDs
- EFLM Papers
- Potentials and pitfalls of ChatGPT and natural-language artificial intelligence models for the understanding of laboratory medicine test results. An assessment by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Artificial Intelligence (WG-AI)
- Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP
- Analytical aspects of the antinuclear antibody test by HEp-2 indirect immunofluorescence: EFLM report on an international survey
- Guidelines and Recommendations
- Variability of cardiac troponin levels in normal subjects and in patients with cardiovascular diseases: analytical considerations and clinical relevance
- General Clinical Chemistry and Laboratory Medicine
- Pre-analytical long-term stability of neopterin and neurofilament light in stored cerebrospinal fluid samples
- Development of a candidate reference measurement procedure by ID-LC-MS/MS for total tau protein measurement in cerebrospinal fluid (CSF)
- Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
- Surface plasmon resonance assays for the therapeutic drug monitoring of infliximab indicate clinical relevance of anti-infliximab antibody binding properties
- An antibody-free LC-MS/MS method for the quantification of sex hormone binding globulin in human serum and plasma
- Accurate stratification between VEXAS syndrome and differential diagnoses by deep learning analysis of peripheral blood smears
- Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups
- Clinical implication by differential analytical performances of serum free light chain quantitation analysis using fully automated analyzers
- Simultaneous analysis of antihyperglycemic small molecule drugs and peptide drugs by means of dual liquid chromatography high-resolution mass spectrometry
- Reference Values and Biological Variations
- Reference intervals for thyroid biomarkers to enhance the assessment of thyroid status in childhood and adolescence
- Biological variation of CA 15-3, CA 125 and HE 4 on lithium heparinate plasma in apparently healthy Caucasian volunteers
- Cancer Diagnostics
- Individual risk prediction of high grade prostate cancer based on the combination between total prostate-specific antigen (PSA) and free to total PSA ratio
- Cardiovascular Diseases
- Using logistic regression models to investigate the effects of high-sensitivity cardiac troponin T confounders on ruling in acute myocardial infarction
- Infectious Diseases
- Assessment of humoral and cellular immunity after bivalent BNT162b2 vaccination and potential association with reactogenicity
- Three rounds of a national external quality assessment reveal a link between disharmonic anti-SARS-CoV-2 antibody quantifications and the infection stage
- Corrigendum
- Where is laboratory medicine headed in the next decade? Partnership model for efficient integration and adoption of artificial intelligence into medical laboratories
- Letters to the Editor
- Please do not call it Theranos
- Lot-to-lot bias for high-sensitivity cardiac troponin I concentrations ≥1000 ng/L
- Lot-to-lot reagent changes and commutability of quality testing materials for total bile acid measurements
- On the importance of sampling interval in studies of biological variation in thyroid function
- Stability of plasma renin concentration based on plasma freezing time, as an adjunct to the stability data reported in the paper by Hepburn and others
- Falsely low beta-hCG results in pregnant woman on Siemens Atellica: don’t forget the “hook effect”
- Proenkephalin A 119–159 (penKid) – a novel biomarker and its quantification on the Nexus IB10 POC system for assessing kidney function
- Investigating the polyuria-polydipsia syndrome: the “PP” Shiny app
- Evaluation of a novel, stand-alone system to measure interleukin-6
- Spurious low WBC count in the WNR channel of Sysmex XN-9000 hematology analyzer in a case with leukocyte aggregation
Artikel in diesem Heft
- Frontmatter
- Editorial
- ChatGPT: Angel or Demond? Critical thinking is still needed
- Mini Review
- Diagnostic accuracy of Siemens SARS-CoV-2 Antigen (CoV2Ag) chemiluminescent immunoassay for diagnosing acute SARS-CoV-2 infection: a pooled analysis
- Opinion Papers
- Neurofilament light chain as neuronal injury marker – what is needed to facilitate implementation in clinical laboratory practice?
- Clinical evidence requirements according to the IVDR 2017/746: practical tools and references for underpinning clinical evidence of IVD-MDs
- EFLM Papers
- Potentials and pitfalls of ChatGPT and natural-language artificial intelligence models for the understanding of laboratory medicine test results. An assessment by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Artificial Intelligence (WG-AI)
- Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP
- Analytical aspects of the antinuclear antibody test by HEp-2 indirect immunofluorescence: EFLM report on an international survey
- Guidelines and Recommendations
- Variability of cardiac troponin levels in normal subjects and in patients with cardiovascular diseases: analytical considerations and clinical relevance
- General Clinical Chemistry and Laboratory Medicine
- Pre-analytical long-term stability of neopterin and neurofilament light in stored cerebrospinal fluid samples
- Development of a candidate reference measurement procedure by ID-LC-MS/MS for total tau protein measurement in cerebrospinal fluid (CSF)
- Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
- Surface plasmon resonance assays for the therapeutic drug monitoring of infliximab indicate clinical relevance of anti-infliximab antibody binding properties
- An antibody-free LC-MS/MS method for the quantification of sex hormone binding globulin in human serum and plasma
- Accurate stratification between VEXAS syndrome and differential diagnoses by deep learning analysis of peripheral blood smears
- Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups
- Clinical implication by differential analytical performances of serum free light chain quantitation analysis using fully automated analyzers
- Simultaneous analysis of antihyperglycemic small molecule drugs and peptide drugs by means of dual liquid chromatography high-resolution mass spectrometry
- Reference Values and Biological Variations
- Reference intervals for thyroid biomarkers to enhance the assessment of thyroid status in childhood and adolescence
- Biological variation of CA 15-3, CA 125 and HE 4 on lithium heparinate plasma in apparently healthy Caucasian volunteers
- Cancer Diagnostics
- Individual risk prediction of high grade prostate cancer based on the combination between total prostate-specific antigen (PSA) and free to total PSA ratio
- Cardiovascular Diseases
- Using logistic regression models to investigate the effects of high-sensitivity cardiac troponin T confounders on ruling in acute myocardial infarction
- Infectious Diseases
- Assessment of humoral and cellular immunity after bivalent BNT162b2 vaccination and potential association with reactogenicity
- Three rounds of a national external quality assessment reveal a link between disharmonic anti-SARS-CoV-2 antibody quantifications and the infection stage
- Corrigendum
- Where is laboratory medicine headed in the next decade? Partnership model for efficient integration and adoption of artificial intelligence into medical laboratories
- Letters to the Editor
- Please do not call it Theranos
- Lot-to-lot bias for high-sensitivity cardiac troponin I concentrations ≥1000 ng/L
- Lot-to-lot reagent changes and commutability of quality testing materials for total bile acid measurements
- On the importance of sampling interval in studies of biological variation in thyroid function
- Stability of plasma renin concentration based on plasma freezing time, as an adjunct to the stability data reported in the paper by Hepburn and others
- Falsely low beta-hCG results in pregnant woman on Siemens Atellica: don’t forget the “hook effect”
- Proenkephalin A 119–159 (penKid) – a novel biomarker and its quantification on the Nexus IB10 POC system for assessing kidney function
- Investigating the polyuria-polydipsia syndrome: the “PP” Shiny app
- Evaluation of a novel, stand-alone system to measure interleukin-6
- Spurious low WBC count in the WNR channel of Sysmex XN-9000 hematology analyzer in a case with leukocyte aggregation
