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Measurement of free light chains – pros and cons of current methods

  • Maria Stella Graziani EMAIL logo
Published/Copyright: January 21, 2016
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 6

Abstract

The measurement of the serum free light chains (FLC) is of paramount importance in the management of patients with plasma cell dyscrasias (PSD). The immunoassays for FLC measurement require adequate precision, accuracy, specificity and reproducibility between batches to prevent under or over estimation of FLC concentration and for an adequate patient monitoring. Considering the peculiarity of the measurand (monoclonal proteins), the optimization of any analytical aspect is difficult to achieve. Three methods are currently available for the assay. The first one has been on the market for over 15 years, and it is based on polyclonal antibodies. The vast majority of the clinical studies demonstrating the utility of the serum FLC measurement have been performed using this assay. A second method based on monoclonal antibodies (mAbs) was marketed in 2011; a third one, also employing mAbs and allowing the simultaneous measurement of κ and λ FLC is in the process of publication. These methods show relevant differences in the type of antibodies used and in the assay design and it is not possible to identify an immunoassay that is superior to the others in any analytical aspect. The comparison studies show that the three methods differ significantly in terms of quantitative values, especially when samples containing monoclonal proteins are compared. Hence the methods cannot be used interchangeably, in particular when the assay is used to monitor the patient response to therapy. In the absence of an international standard for FLC measurement, it is impossible, at this stage to establish, which method shows the best accuracy.

Keywords: free light chain assays; immunoassays; method comparison; plasma cell dyscrasias
Corresponding author: Maria Stella Graziani, University Hospital of Verona, piazzale Stefani, 1 Verona, VR 37126, Italy

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Received: 2015-10-31
Accepted: 2015-12-9
Published Online: 2016-1-21
Published in Print: 2016-6-1

©2016 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
  4. Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
  5. Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
  6. Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
  7. Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
  8. The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
  9. Serum and Urine Protein Electrophoresis and Immunofixation Testing
  10. Challenges of measuring monoclonal proteins in serum
  11. Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
  12. Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
  13. Moving towards harmonized reporting of serum and urine protein electrophoresis
  14. Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
  15. Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
  16. New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
  17. Serum Free Light Chain Methods and Controversies
  18. Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
  19. Measurement of free light chains with assays based on monoclonal antibodies
  20. Measurement of free light chains – pros and cons of current methods
  21. Is accuracy of serum free light chain measurement achievable?
  22. Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
  23. A patient with AL amyloidosis with negative free light chain results
  24. Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
  25. Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
  26. New Laboratory Assays and Challenges
  27. Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
  28. Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
  29. Free light chains and heavy/light chains in monitoring POEMS patients
  30. Monitoring free light chains in serum using mass spectrometry
  31. Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
  32. Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
  33. Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
  34. Letter to the Editor
  35. Discrepancy between FLC assays: only a problem of quantification?
https://doi.org/10.1515/cclm-2015-1062
Keywords for this article
free light chain assays; immunoassays; method comparison; plasma cell dyscrasias

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
  4. Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
  5. Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
  6. Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
  7. Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
  8. The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
  9. Serum and Urine Protein Electrophoresis and Immunofixation Testing
  10. Challenges of measuring monoclonal proteins in serum
  11. Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
  12. Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
  13. Moving towards harmonized reporting of serum and urine protein electrophoresis
  14. Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
  15. Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
  16. New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
  17. Serum Free Light Chain Methods and Controversies
  18. Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
  19. Measurement of free light chains with assays based on monoclonal antibodies
  20. Measurement of free light chains – pros and cons of current methods
  21. Is accuracy of serum free light chain measurement achievable?
  22. Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
  23. A patient with AL amyloidosis with negative free light chain results
  24. Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
  25. Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
  26. New Laboratory Assays and Challenges
  27. Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
  28. Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
  29. Free light chains and heavy/light chains in monitoring POEMS patients
  30. Monitoring free light chains in serum using mass spectrometry
  31. Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
  32. Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
  33. Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
  34. Letter to the Editor
  35. Discrepancy between FLC assays: only a problem of quantification?
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