Performance Characteristics and Limitations of the Available Assays for the Detection and Quantitation of Monoclonal Free Light Chains and New Emerging Methodologies
Abstract
:1. Introduction
2. Laboratory Assays for the Detection and Measurement of Monoclonal FLC in Patients with Plasma Cell Dyscrasias and Their Strengths and Limitations
2.1. Urine Protein Electrophoresis and Urine Immunofixation for the Detection and Measurement of Monoclonal FLC (Bence Jones Protein) in Urine
2.2. Modifications to Enhance the Sensitivity of Serum IFE
2.3. Serum FLC Assays
The Spectrum of Commercially Available Serum FLC Assays
2.4. Mass Spectrometry-Based Assays for the Detection of Monoclonal FLC
2.5. Isoelectric Focussing
2.6. Amylite
3. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Assay Name | Antisera | Testing Methodology | FLC Reference Ranges (mg/L) | FLC Ratio Reference Range |
---|---|---|---|---|
Freelite [61,62] | Polyclonal | Turbidimetry/ nephelometry | Kappa 3.3–19.4 | 0.26–1.65 |
Lambda 5.7–26.3 | ||||
Sebia FLC [55] | Polyclonal | ELISA | Kappa 6.4–17.4 | 0.46–1.51 |
Lambda 8.4–21.8 | ||||
Diazyme [47,62] | Polyclonal | Turbidimetry | Kappa 2.37–20.73 | 0.22–1.74 |
Lambda 4.23–27.69 | ||||
Kloneus Free Light Chain [62] | Polyclonal | Turbidimetry/nephelometry | Kappa 3.3–19.4 | 0.26–1.65 |
Lambda 5.7–26.3 | ||||
Seralite [57] | Monoclonal | Competitive inhibition | Kappa 5.3–22.7 | 0.5–2.5 |
immunochromatography | Lambda 4.0–25.1 | |||
N Latex FLC [57] | Monoclonal | Nephelometry | Kappa 6.7–22.4 | 0.31–1.56 |
Lambda 8.3–27.0 |
Method | Approved Applications | Advantages | Disadvantages |
---|---|---|---|
SPE and sIFE | Monitoring patients with MGUS, multiple myeloma, and AL amyloidosis [31,33] | Widely available | Low sensitivity compared to FLC-specific assays [26] |
Relatively low cost | Not used for quantitative assessment of FLC monoclonal proteins | ||
uPE and uIFE | Response assessment in patients with multiple myeloma and AL amyloidosis [31,33] | Widely available | False positives for BJP in patients with chronic kidney disease [100] |
≥500 mg/24 h BJP differentiates myeloma from MGUS in the IMWG diagnostic criteria [31] | Relatively low cost | Requires a 24 h urine collection | |
Serum FLC assays | Response assessment in patients with multiple myeloma and AL amyloidosis [5,31,33] | Widely available | No international consensus on the most appropriate reference range to use in patients with varying degrees of renal impairment |
Risk stratification of patients with MGUS, SMM and AL amyloidosis [43,44,45] | Provides additional sensitivity for the detection of low-level monoclonal FLC in patients with FLC myeloma and AL amyloidosis [5,26,36] | Rely on the ratio between the uninvolved and involved FLC as an indirect indicator of clonality, which can lead to false positives in the presence of oligoclonal immune reconstitution and/or treatment related immune suppression [101] | |
The level of the involved FLC helps identify patients with myeloma and renal impairment who are likely to have renal impairment due to cast nephropathy [12,13,102] | Automated sample processing and result generation | ||
FLC ratio ≥100 is incorporated into the SLiM CRAB criteria for the identification of patients with symptomatic multiple myeloma [30] | Convenient -analysis can be performed on the same sample used for SPE and sIFE | ||
Intact light chain MS assays | In lieu of immunofixation in patients with multiple myeloma and related disorders [3] | Greater sensitivity compared to sIFE [91,94,103] | More expensive than the electrophoretic assays and serum FLC assays [92] |
Tracking the monoclonal protein using its isotype and mass-to-charge ratio enables more reliable differentiation between oligoclonal peaks and residual low-level monoclonal protein monoclonal protein | The availability of the intact light chain assays is limited: EXENT is currently only approved for use in Europe; MASS-FIX is only available for use in Europe; and FLC-MS is not currently approved for clinical use | ||
High sample throughput possible due to automated sample processing and semi- or fully automated result interpretation depending on the assay used [93] | Risk of missing low-level FLC-only monoclonal protein if sFLC and uIFE are not used alongside MS assays that only include total light chain-specific reagents [96] | ||
Able to identify post-translational modifications such as N-linked glycosylation [92,96,103] | MASS-FIX and EXENT only provide a qualitative assessment about the presence absence of monoclonal light chains (FLC-MS could provide quantitative assessments but is currently only a research tool) |
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Giles, H.V.; Karunanithi, K. Performance Characteristics and Limitations of the Available Assays for the Detection and Quantitation of Monoclonal Free Light Chains and New Emerging Methodologies. Antibodies 2024, 13, 19. https://doi.org/10.3390/antib13010019
Giles HV, Karunanithi K. Performance Characteristics and Limitations of the Available Assays for the Detection and Quantitation of Monoclonal Free Light Chains and New Emerging Methodologies. Antibodies. 2024; 13(1):19. https://doi.org/10.3390/antib13010019
Chicago/Turabian StyleGiles, Hannah V., and Kamaraj Karunanithi. 2024. "Performance Characteristics and Limitations of the Available Assays for the Detection and Quantitation of Monoclonal Free Light Chains and New Emerging Methodologies" Antibodies 13, no. 1: 19. https://doi.org/10.3390/antib13010019