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Farnsworth CW, Logsdon NM, Hayes JE, Rais R, Willrich MA, Gronowski AM. Limitations of Free Light Chain Assays caused by the Matrix Effect. J Appl Lab Med 2021; 5:311-319. [PMID: 32445382 DOI: 10.1093/jalm/jfz021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 10/01/2019] [Indexed: 11/12/2022]
Abstract
BACKGROUND Serum free light chain (FLC) assays are used clinically to measure the concentration of κ and λ FLC in patients with suspected or diagnosed plasma cell proliferative disorders. Previous studies have demonstrated a loss of linearity in low concentration ranges of these assays. We hypothesized that this result could be caused by a matrix effect. METHODS Recovery studies were performed for κ and λ FLC in both serum and saline using the Freelite assay (Binding Site) on a Cobas c502 system (Roche). Samples were analyzed either at the recommended dilution or undiluted. Follow-up studies were performed in varying matrices ranging from 0% to 100% saline. Retrospective patient data were analyzed to assess the impact on reported κ FLC, λ FLC, and κ/λ ratio. RESULTS FLC in a serum matrix demonstrated underrecovery relative to samples diluted in saline for both κ and λ FLC. Of 255 patient samples with λ FLC measured undiluted (λ FLC <6.0 mg/L), an unexpected gap was observed in patient results between 2.0 and 6.0 mg/L. In addition, 23 patients measured serially with λ FLC between 2.0 and 6.0 mg/L demonstrated dramatic changes in κ/λ ratio, with no changes in κ FLC, likely because of the matrix effect. CONCLUSIONS The κ and λ Freelite assays exhibit a matrix effect when samples are tested undiluted, which has the potential to affect the κ/λ ratio. Consequently, our laboratory has stopped reporting λ FLC <6.0 mg/L.
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Affiliation(s)
- Christopher W Farnsworth
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University, St. Louis, MO
| | | | | | - Rehan Rais
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University, St. Louis, MO
| | - Maria A Willrich
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Ann M Gronowski
- Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University, St. Louis, MO
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Dong X, Zhang Z, Shou L, Shen J. Interleukin-6 gene-174 G/C promoter polymorphism is not associated with multiple myeloma susceptibility: evidence from meta-analysis: A systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e24647. [PMID: 33578591 PMCID: PMC10545425 DOI: 10.1097/md.0000000000024647] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 01/06/2021] [Accepted: 01/11/2021] [Indexed: 01/05/2023] Open
Abstract
PURPOSE Presently, whether interleukin-6 (IL-6) gene-174 G/C promoter polymorphism is correlated to the susceptibility of multiple myeloma (MM) remains controversial. For this reason, the method of meta-analysis was applied to exploring the association between IL-6 gene-174 G/C promoter polymorphism and MM. METHOD Two independent researchers systematically searched PubMed, EMBASE, Google academic, Cochrane Library and Chinese literature databases to screen case-control studies on IL-6 gene-174 G/C promoter polymorphism and MM susceptibility. The retrieval period was limited from the formation of the database to January 2020, and data analysis was conducted by employing Stata 11.0 software. RESULT Seven articles were ultimately included in the present study, including 594 MM patients and 681 controls. Integration analysis exhibited that compared with GC or CC genotype, GG genotype did not increase MM susceptibility (OR = 0.95, 95% CI 0.75-1.22; OR = 0.79, 95% CI 0.52-1.19, respectively). Further, in comparison with CC genotype, GC genotype also presented no effect on increasing MM susceptibility (OR = 0.79, 95% CI 0.53-1.16), while compared with GC+CC genotype, GG genotype had no significant relationship with MM susceptibility (OR = 0.94, 95% CI 0.75-1.19). In subsequent analysis, an observation was made that allele G or C was not related to MM susceptibility (OR = 0.92, 95% CI 0.76-1.12). Funnel chart and Begg test did not reveal publication bias in the included articles. CONCLUSION The results of the present study advocate that there is no testimony to support the relationship between IL-6 gene-174 G/C promoter polymorphism and MM susceptibility.
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Affiliation(s)
| | - Zongxin Zhang
- Clinical Laboratory, Huzhou Central Hospital, Affiliated Cent Hospital Huzhou University, No. 1558, Sanhuanbei Road, Wuxing district, Huzhou, Zhejiang, PR China
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Zaydman MA, Brestoff JR, Logsdon N, Gronowski AM. Kinetic Approach Extends the Analytical Measurement Range and Corrects Antigen Excess in Homogeneous Turbidimetric Immunoassays. J Appl Lab Med 2019; 4:214-223. [PMID: 31639666 DOI: 10.1373/jalm.2019.029256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 05/06/2019] [Indexed: 11/06/2022]
Abstract
BACKGROUND Homogeneous turbidimetric immunoassays are widely used in the clinical laboratory and offer short assay times, reduced reagent costs, and the potential for full automation. However, these assays have a limited analytical measurement range (AMR) above which antigen excess leads to falsely low estimates of the analyte concentration (i.e., the hook effect). Traditional methods for correction of antigen excess require sample dilution, compromising time and cost-efficiency. Therefore, novel methods that extend the AMR are needed. METHODS A kinetic model of a generic homogeneous turbidimetric immunoassay was built and then parameterized using a genetic algorithm. Kinetic features that could be used to extend the AMR were identified and subsequently validated with clinical data from consecutive measurements of 2 homogeneous turbidimetric immunoassays: κ serum free light chain and rheumatoid factor. RESULTS A novel kinetic parameter, the area under the curvature (AUCU), was derived that increases in proportion to the analyte concentration in a range beyond the AMR of conventional end point methods. When applied to clinical data, the AUCU method provided a log-linear calibration curve in the zone of antigen excess extending the AMR by >10-fold for 2 different immunoassays. CONCLUSIONS The AUCU method detects and corrects antigen excess, extending the AMR in homogeneous turbidimetric immunoassays. The advantage of this method over conventional methods would be a reduction in the number of repeated samples, resulting in significant time and cost savings.
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Affiliation(s)
- Mark A Zaydman
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO;
| | - Jonathan R Brestoff
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
| | | | - Ann M Gronowski
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
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Lutteri L, Aldenhoff MC, Cavalier E. Evaluation of the new Sebia free light chain assay using the AP22 ELITE instrument. Clin Chim Acta 2018; 487:161-167. [DOI: 10.1016/j.cca.2018.09.030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 09/18/2018] [Accepted: 09/18/2018] [Indexed: 11/29/2022]
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Bossuyt X, Delforge M, Reynders M, Dillaerts D, Sprangers B, Fostier K, Poesen K, Vercammen M. Antigen excess detection by automated assays for free light chains. Clin Chem Lab Med 2018; 56:e235-e238. [PMID: 29679525 DOI: 10.1515/cclm-2017-0977] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 02/16/2018] [Indexed: 11/15/2022]
Affiliation(s)
- Xavier Bossuyt
- Laboratory Medicine, University Hospitals Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium, Phone: +32 16 347009, Fax: +32 16 34 79 31.,Laboratory Medicine, Immunology, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, Experimental Laboratory Immunology, Catholic University of Leuven, Leuven, Belgium
| | | | - Martin Reynders
- Laboratory Medicine, Immunology, University Hospitals Leuven, Leuven, Belgium
| | - Doreen Dillaerts
- Department of Microbiology and Immunology, Experimental Laboratory Immunology, Catholic University of Leuven, Leuven, Belgium
| | - Ben Sprangers
- Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Karel Fostier
- Hematology, University Hospital VUB, Brussels, Belgium
| | - Koen Poesen
- Laboratory Medicine, Immunology, University Hospitals Leuven, Leuven, Belgium.,Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven, Belgium
| | - Martine Vercammen
- Department of Laboratory Medicine, AZ Sint-Jan, Brugge, Belgium (actual).,Laboratory of Hematology, Universitair Ziekenhuis Brussel VUB, Brussels, Belgium (former)
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Cast Nephropathy and Deceptively Low Absolute Serum Free Light Chain Levels: Resolution of a Challenging Case and Systematic Review of the Literature. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2017; 18:e1-e7. [PMID: 29066226 DOI: 10.1016/j.clml.2017.09.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Revised: 08/14/2017] [Accepted: 09/25/2017] [Indexed: 11/22/2022]
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Evaluation of a new free light chain ELISA assay: bringing coherence with electrophoretic methods. ACTA ACUST UNITED AC 2017; 56:312-322. [DOI: 10.1515/cclm-2017-0339] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 07/06/2017] [Indexed: 01/08/2023]
Abstract
Abstract
Background:
Serum free light chain (sFLC) measurements are increasingly important in the context of screening for monoclonal gammopathies, prognostic stratification, and monitoring of therapy responses. At the same time, analytical limitations have been reported with the currently available nephelometric and turbidimetric sFLC assays. We have evaluated a new quantitative sFLC ELISA for its suitability in routine clinical use.
Methods:
Reference ranges of the Sebia FLC assay were calculated from 208 controls. Assay interference, reproducibility, lot-to-lot variability, and linearity were assessed. Method comparison to the Freelite assay (Binding Site) was conducted by retrospective analysis of 501 patient sera.
Results:
Reference ranges of the Sebia κ/λFLC-ratio were 0.37–1.44. We observed good sensitivity (1.5 mg/L) and linearity in both polyclonal and monoclonal sFLC samples and never experienced antigen excess. Sebia FLC reproducibility varied between 6.7% and 8.1% with good lot-to-lot consistency. Method comparison with Freelite showed the following correlations: κFLC R=0.94, λFLC R=0.92 and κ/λFLC-ratio R=0.96. The clinical concordance of the κ/λFLC-ratio of both methods was 94%. Significant quantitative differences were observed between both methods, mainly in sera with high FLC concentrations. The Sebia monoclonal FLC concentrations were coherent with those obtained by serum protein electrophoresis (SPE). Freelite monoclonal FLC concentrations were consistently higher, with a mean 12-fold overestimation compared to SPE.
Conclusions:
The Sebia FLC assay provides a novel platform for sensitive and accurate sFLC measurements. The Sebia FLC showed good clinical concordance with Freelite. Further studies are warranted to confirm the clinical value of this assay.
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Jacobs JFM, Tate JR, Merlini G. Is accuracy of serum free light chain measurement achievable? Clin Chem Lab Med 2017; 54:1021-30. [PMID: 26641970 DOI: 10.1515/cclm-2015-0879] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Accepted: 11/06/2015] [Indexed: 11/15/2022]
Abstract
The serum free light chain (FLC) assay has proven to be an important complementary test in the management of patients with monoclonal gammopathies. The serum FLC assay has value for patients with plasma cell disorders in the context of screening and diagnosis, prognostic stratification, and quantitative monitoring. Nonetheless, serum FLC measurements have analytical limitations which give rise to differences in FLC reporting depending on which FLC assay and analytical platform is used. As the FLC measurements are incorporated in the International Myeloma Working Group guidelines for the evaluation and management of plasma cell dyscrasias, this may directly affect clinical decisions. As new certified methods for serum FLC assays emerge, the need to harmonise patient FLC results becomes increasingly important. In this opinion paper we provide an overview of the current lack of accuracy and harmonisation in serum FLC measurements. The clinical consequence of non-harmonized FLC measurements is that an individual patient may or may not meet certain diagnostic, prognostic, or response criteria, depending on which FLC assay and platform is used. We further discuss whether standardisation of serum FLC measurements is feasible and provide an overview of the steps needed to be taken towards harmonisation of FLC measurements.
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Campbell JP, Heaney JL, Shemar M, Baldwin D, Griffin AE, Oldridge E, Goodall M, Afzal Z, Plant T, Cobbold M, Jefferis R, Jacobs JF, Hand C, Drayson MT. Development of a rapid and quantitative lateral flow assay for the simultaneous measurement of serum κ and λ immunoglobulin free light chains (FLC): inception of a new near-patient FLC screening tool. ACTA ACUST UNITED AC 2017; 55:424-434. [DOI: 10.1515/cclm-2016-0194] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 07/07/2016] [Indexed: 12/23/2022]
Abstract
AbstractBackground:Serum free light chains (FLC) are sensitive biomarkers used for the diagnosis and management of plasma cell dyscrasias, such as multiple myeloma (MM), and are central to clinical screening algorithms and therapy response criteria. We have developed a portable, near-patient, lateral-flow test (SeraliteMethods:Assay interference, imprecision, lot-to-lot variability, linearity, and the utility of a competitive-inhibition design for the elimination of antigen-excess (‘hook effect’) were assessed. Reference ranges were calculated from 91 healthy donor sera. Preliminary clinical validation was conducted by retrospective analysis of sera from 329 patients. Quantitative and diagnostic results were compared to FreeliteResults:SeraliteConclusions:Seralite
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Keren DF, Schroeder L. Challenges of measuring monoclonal proteins in serum. ACTA ACUST UNITED AC 2016; 54:947-61. [DOI: 10.1515/cclm-2015-0862] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Accepted: 01/06/2016] [Indexed: 01/16/2023]
Abstract
AbstractThe measurement of monoclonal protein (M-protein) is vital for stratifying risk and following individuals with a variety of monoclonal gammopathies. Direct measurement of the M-protein spike by electrophoresis and immunochemical measurements of specific isotypes or free light chains pairs has provided useful information about the quantity of M-protein. Nonetheless, both traditional electrophoresis and immunochemical methods give poor quantification with M-proteins smaller than 10 g/L (1 g/dL) when in the presence of polyclonal immunoglobulins that co-migrate with the M-protein. In addition, measurements by electrophoresis of M-proteins migrating in the β- and α-regions are contaminated by normal serum proteins in those regions. The most precise electrophoretic method to date for quantification involves exclusion of the polyclonal immunoglobulins by using the tangent skimming method on electropherograms, which provides a 10-fold improvement in precision. So far, however, tangent measurements are limited to γ migrating M-proteins. Another way to improve M-protein measurements is the use of capillary electrophoresis (CE). With CE, one can employ immunosubtraction to select a region of interest in the β region thereby excluding much of the normal proteins from the M-protein measurement. Recent development of an immunochemical method distinguishing heavy/light chain pairs (separately measuring IgGK and IgGL, IgAK and IgAL, and IgMK and IgML) provides measurements that could exclude polyclonal contaminants of the same heavy chain with the uninvolved light chain type. Yet, even heavy/light results contain an immeasurable quantity of polyclonal heavy/light chains of the involved isotype. Finally, use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) looms on the horizon as a means to provide more consistent and sensitive measurements of M-proteins.
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Carr-Smith HD, Jenner EL, Evans JA, Harding SJ. Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents. ACTA ACUST UNITED AC 2016; 54:997-1003. [DOI: 10.1515/cclm-2015-1068] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 01/21/2016] [Indexed: 11/15/2022]
Abstract
AbstractSerum free light chain (FLC) assays have been incorporated into routine clinical practice and their use is recommended in international guidelines for the management of monoclonal gammopathies. Given that FLCs are not simple analytes, laboratories should be aware of potential analytical issues when using FLC assays, including antigen excess, lot-to-lot variation and non-linearity. Whilst manufacturers of monoclonal antibody-based assays claim that they overcome such issues, the evidence available to date does not support this. Here we review and compare the technical performance of both polyclonal and monoclonal antibody-based assays. The evidence suggests that the Freelite assay, based on polyclonal antisera, gives a broader recognition of monoclonal FLCs than the N Latex assay, based on monoclonal antisera, and despite being cited as a technical concern, we show that lot-to-lot variation of the Freelite assay is good. Both non-linearity and antigen excess are characteristic of FLC analysis and laboratories should be aware of these phenomena regardless of the assay system they use. Comparisons of the absolute values of sFLCs determined using monoclonal and polyclonal antibody-based assays show poor quantitative agreement and, because current guidelines have been established using the polyclonal antibody-based Freelite assay, it should not be assumed that assays utilizing monoclonal antibodies will give compliance with these guidelines.
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12
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Vercammen MJ, Broodtaerts L, Meirlaen P, Bossuyt X. Overestimation of free light chain antigen excess rate. Clin Chim Acta 2015; 444:297-302. [DOI: 10.1016/j.cca.2015.02.047] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Accepted: 02/26/2015] [Indexed: 12/26/2022]
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13
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Jacobs JF, van der Molen RG, Bossuyt X, Damoiseaux J. Antigen excess in modern immunoassays: To anticipate on the unexpected. Autoimmun Rev 2015; 14:160-7. [DOI: 10.1016/j.autrev.2014.10.018] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 10/09/2014] [Indexed: 12/17/2022]
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Urdal P, Amundsen EK, Toska K, Klingenberg O. Automated alarm to detect antigen excess in serum free immunoglobulin light chain kappa and lambda assays. Scandinavian Journal of Clinical and Laboratory Investigation 2014; 74:575-81. [PMID: 25007050 DOI: 10.3109/00365513.2014.915426] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Antigen excess causing a falsely low concentration result may occur when measuring serum free immunoglobulin light chains (SFLC). Automated antigen excess detection methods are available only with some analyzers. We have now developed and verified such a method. METHODS Residuals of sera with known SFLC-κ and -λ concentrations were analyzed using Binding Site reagents and methods adapted to the Roche Cobas® c.501 analyzer. RESULTS We analyzed 117 sera for SFLC-κ and -λ and examined how the absorbance increased with time during the 7 minutes of reaction (absorbance reading points 12-70). From this an antigen excess alarm factor (ratio of absorbance increases between reading points 68-60 and 20-12, multiplied by 100) was defined. Upon our request, Roche added to our two SFLC assays a program which calculated this antigen excess alarm factor and triggered an alarm when the factor was below a defined value. We verified this antigen excess alarm function by analyzing serum from 325 persons of whom 143 were multiple myeloma patients. All samples with a known concentration above 30 mg/L triggered either an antigen excess alarm, an 'above test' alarm or both. Also, all samples above 200 mg/L (SFLC-λ) and 300 mg/L (SFLC-κ) triggered the antigen excess alarm and all but one triggered the above test alarm. CONCLUSIONS The antigen excess alarm function presented here detected all known antigen excess samples at no increased time of analysis, a reduced workload and reduced reagent cost.
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Affiliation(s)
- Petter Urdal
- Department of Medical Biochemistry, Oslo University Hospital , Ullevål , Norway
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Bhole MV, Sadler R, Ramasamy K. Serum-free light-chain assay: clinical utility and limitations. Ann Clin Biochem 2014; 51:528-42. [PMID: 24489083 DOI: 10.1177/0004563213518758] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
In the last decade, the introduction of the serum-free light-chain (sFLC) assay has been an important advance in the diagnosis and management of plasma cell dyscrasias, particularly monoclonal light-chain diseases. The immunoassay was developed to detect free light chains in serum by using anti-FLC antibodies which specifically recognised epitopes on light chains that were 'hidden' in intact immunoglobulins. Since its introduction in 2001, there have been several publications in the English language literature discussing the clinical utility as well as analytical limitations of the sFLC assay. These studies have highlighted both positive and negative aspects of the assay particularly with regard to its sensitivity and specificity and the technical challenges that can affect its performance. The contribution and significance of the sFLC assay in the management of light-chain myeloma, primary amyloid light-chain (AL) amyloidosis and non-secretory myeloma are well recognised and will be addressed in this review. The aim of this article is to also review the published literature with a view to providing a clear understanding of its utility and limitations in the diagnosis, prognosis and monitoring of plasma dyscrasias including intact immunoglobulin multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS). The increasing interest in using this assay in other haematological conditions will also be briefly discussed.
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Affiliation(s)
- Malini V Bhole
- Department of Immunology, Russells Hall Hospital, The Dudley Group NHS Foundation Trust, Dudley, UK
| | - Ross Sadler
- Department of Immunology, Churchill Hospital, Oxford Radcliffe NHS Trust, Oxford, UK
| | - Karthik Ramasamy
- Department of Haematology, Churchill Hospital, Oxford Radcliffe NHS Trust, Oxford, UK Department of Haematology, Royal Berkshire Hospital NHS Foundation Trust, Reading, UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Headington, UK
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Ozsan GH, Dispenzieri A. Serum free light chain analysis in multiple myeloma and plasma cell dyscrasias. Expert Rev Clin Immunol 2014; 7:65-73. [DOI: 10.1586/eci.10.80] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Graziani MS, Merlini G. Serum free light chain analysis in the diagnosis and management of multiple myeloma and related conditions. Expert Rev Mol Diagn 2013; 14:55-66. [DOI: 10.1586/14737159.2014.864557] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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Maher J. Role of the clinical immunology laboratory in disease monitoring. World J Immunol 2013; 3:18-30. [DOI: 10.5411/wji.v3.i2.18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Accepted: 05/17/2013] [Indexed: 02/05/2023] Open
Abstract
Immunological investigations provide useful information to guide diagnosis of several disorders. Many such tests are also commonly repeated at intervals, in an effort to facilitate disease monitoring. In general however, immunology test results are often slow to alter. Furthermore, audit activity has indicated that repeated testing accounts for a substantial workload in many immunology services, which may waste resources and compromise the efficient completion of necessary tests. Consequently, the need and appropriate minimum interval between repeated testing requires critical evaluation. In this review, the clinical utility of repeated performance of several common immunology investigations has been evaluated, based upon published evidence. In some cases (e.g., paraprotein quantification, or measurement of anti-glomerular basement membrane antibodies), repeated testing provides vital clinical information and can be justified on a frequent and individualized basis. However, many other investigations provided by immunology services provide less valuable information when used to aid disease monitoring rather than diagnosis. It is hoped that the data summarized here will facilitate a more evidence-based approach to repeated testing. Such information may also assist with the local implementation of demand management strategies based upon setting of minimum retesting intervals for these investigations.
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Basu S, Wallage MJ, Lock RJ. Response to Pretorius: ‘Evaluation of the N Latex FLC free light chain assay on the Siemens BN analyser’. Ann Clin Biochem 2013; 50:278-9. [DOI: 10.1177/0004563212473449] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Supratik Basu
- Department of Haematology, Royal Wolverhampton Hospitals, Wolverhampton Road, Wolverhampton WV10 0QP
| | - Michael J Wallage
- Immunology and Immunogenetics, North Bristol NHS Trust, Bristol, BS10 5NB, UK
| | - Robert J Lock
- Immunology and Immunogenetics, North Bristol NHS Trust, Bristol, BS10 5NB, UK
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Campbell JP, Cobbold M, Wang Y, Goodall M, Bonney SL, Chamba A, Birtwistle J, Plant T, Afzal Z, Jefferis R, Drayson MT. Development of a highly-sensitive multi-plex assay using monoclonal antibodies for the simultaneous measurement of kappa and lambda immunoglobulin free light chains in serum and urine. J Immunol Methods 2013; 391:1-13. [DOI: 10.1016/j.jim.2013.01.014] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2012] [Revised: 01/28/2013] [Accepted: 01/28/2013] [Indexed: 12/01/2022]
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Brebner JA, Stockley RA. Polyclonal free light chains: a biomarker of inflammatory disease or treatment target? F1000 MEDICINE REPORTS 2013; 5:4. [PMID: 23413370 PMCID: PMC3564472 DOI: 10.3410/m5-4] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Free light chains are proteins produced by B lymphocytes during the process of antibody synthesis. Their production, as a reflection of B cell activation, can give insight into the activity of the adaptive immune system. In recent years, an automated immunoassay that provides quantitative measurement of free light chains in the serum has been developed. This assay has not only revolutionised the investigation of monoclonal light chain overproduction in plasma cell diseases, but has also allowed for the quantification of polyclonal free light chains in serum. The discovery of high levels of polyclonal free light chains in a number of inflammatory and auto-immune conditions has led to the examination of their value as a biomarker of disease activity. Research into their bio-activity has also highlighted their potential role in the pathogenesis of inflammatory disease, making them an attractive target for novel therapies.
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Affiliation(s)
- Judith A Brebner
- Lung Function and Sleep Department, Queen Elizabeth Hospital Mindelsohn Way, Edgbaston, Birmingham, B15 2WB
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Pretorius CJ, Klingberg S, Tate J, Wilgen U, Ungerer JPJ. Evaluation of the N Latex FLC free light chain assay on the Siemens BN analyser: precision, agreement, linearity and variation between reagent lots. Ann Clin Biochem 2012; 49:450-5. [DOI: 10.1258/acb.2012.011264] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Background The clinical utility of serum κ and λ free light chains (FLC) for the diagnosis and prognosis of plasma cell proliferative disorders is well established. We assessed the analytical performance of the N Latex FLC assays and compared it with the Freelite™ assays. Methods Analytical precision was assessed according to the CLSI EP5-A2 protocol. Method comparison was performed with 116 clinical samples and linearity was assessed on samples with monoclonal and polyclonal elevations of FLC. Analytical bias and variance was measured with two lots of N Latex FLC reagent. Results The N Latex FLC κ and λ assays had a total coefficient of variation of 5–7% across the analytical range. The slopes were 1.36 and 1.37 and the between-method variances were 40.0% and 45.4%, respectively, compared with the Freelite™. Good agreement in classification was observed for κ, λ and the κ/ λ ratio (Cohen's κ 0.84, 0.76 and 0.89). Statistical non-linearity occurred commonly, but clinically significant non-linearity was observed in only one instance. Between-reagent lot variation was 7.3% and 10% for κ and λ, respectively. Conclusions The N Latex FLC assay has good precision, did not exhibit gross antigen excess and can be used in clinical practice based on the analytical performance characteristics.
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Affiliation(s)
- Carel J Pretorius
- Department of Chemical Pathology, Pathology Queensland, Brisbane 4029, Queensland, Australia
| | - Sandra Klingberg
- Department of Chemical Pathology, Pathology Queensland, Brisbane 4029, Queensland, Australia
| | - Jill Tate
- Department of Chemical Pathology, Pathology Queensland, Brisbane 4029, Queensland, Australia
| | - Urs Wilgen
- Department of Chemical Pathology, Pathology Queensland, Brisbane 4029, Queensland, Australia
| | - Jacobus P J Ungerer
- Department of Chemical Pathology, Pathology Queensland, Brisbane 4029, Queensland, Australia
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Antigen excess and non-linearity of serum free light chain measurements. Clin Chim Acta 2012. [DOI: 10.1016/j.cca.2012.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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24
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Serum free light chain immunoassays: A guide to antigen excess detection. Clin Chim Acta 2012; 413:949; author reply 952. [DOI: 10.1016/j.cca.2012.01.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2011] [Accepted: 01/15/2012] [Indexed: 11/18/2022]
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25
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Effect of sample dilution on serum free light chain concentration by immunonephelometric assay. Clin Chim Acta 2011; 412:1798-804. [DOI: 10.1016/j.cca.2011.06.021] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Revised: 06/01/2011] [Accepted: 06/01/2011] [Indexed: 11/22/2022]
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26
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Levinson SS. Hook effect with lambda free light chain in serum free light chain assay. Clin Chim Acta 2010; 411:1834-6. [PMID: 20667445 DOI: 10.1016/j.cca.2010.07.027] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2010] [Revised: 07/16/2010] [Accepted: 07/19/2010] [Indexed: 11/27/2022]
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27
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Bosmann M, Kößler J, Stolz H, Walter U, Knop S, Steigerwald U. Detection of serum free light chains: the problem with antigen excess. Clin Chem Lab Med 2010; 48:1419-22. [DOI: 10.1515/cclm.2010.283] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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