scholarly journals Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies

2016 ◽  
Vol 54 (6) ◽  
Author(s):  
Jillian R. Tate ◽  
Maria Stella Graziani ◽  
Peter Mollee ◽  
Giampaolo Merlini
Keyword(s):  
Plasma Cell ◽  
Laboratory Testing ◽  
Protein Electrophoresis ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Plasma Cell Disorders ◽  
Serum Free Light Chains

Quantification by Ultrafiltration and Immunofixation Electrophoresis Testing for Monoclonal Serum Free Light Chains

2020 ◽  
Vol 51 (6) ◽  
pp. 592-600 ◽  
Author(s):  
Gurmukh Singh ◽  
Roni Bollag
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Limit Of Detection ◽  
Light Chains ◽  
Total Serum ◽  
Reliable Estimate ◽  
Free Light Chains ◽  
Serum Free ◽  
Immunofixation Electrophoresis ◽  
Serum Free Light Chains

Abstract Objective Measurement of monoclonal immunoglobulins is a reliable estimate of the plasma cell tumor mass. About 15% of plasma cell myelomas secrete light chains only. The concentration of serum free light chains is insufficient evidence of the monoclonal light chain burden. A sensitive quantitative estimate of serum free monoclonal light chains could be useful for monitoring patients with light chain myeloma. We describe such an assay that does not require mass-spectrometry equipment or expertise. Methods Serum specimens from patients with known light chain myelomas and controls were subjected to ultrafiltration through a membrane with pore size of 50 kDa. The filtrate was concentrated and tested by immunofixation electrophoresis. The relative area under the monoclonal peak, compared to that of the total involved light chain composition, was estimated by densitometric scanning of immunofixation gels. The proportion of the area occupied by the monoclonal peak in representative densitometric scans was used to arrive at the total serum concentration of the monoclonal serum free light chains. Results Using an ultracentrifugation and concentration process, monoclonal serum free light chains were detectable, along with polyclonal light chains, in all 10 patients with active light chain myelomas. Monoclonal light chains were identified in serum specimens that did not reveal monoclonal light chains by conventional immunofixation electrophoresis. The limit of detection by this method was 1.0 mg/L of monoclonal serum free light chains. Conclusion The method described here is simple enough to be implemented in academic medical center clinical laboratories and does not require special reagents, equipment, or expertise. Even though urine examination is the preferred method for the diagnosis of light chain plasma cell myelomas, measurement of the concentration of serum free light chains provides a convenient, albeit inadequate, way to monitor the course of disease. The method described here allows effective electrophoretic differentiation of monoclonal serum free light chain from polyclonal serum free light chains and provides a quantitation of the monoclonal serum free light chains in monitoring light chain monoclonal gammopathies.

scholarly journals Recommendations for Use of Free Light Chain Assay in Monoclonal Gammopathies

2010 ◽  
Vol 29 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Vesna Radović
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
High Sensitivity ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Bone Marrow Biopsies ◽  
Monoclonal Gammopathies ◽  
Plasma Cell Disorders

Recommendations for Use of Free Light Chain Assay in Monoclonal GammopathiesThe serum immunoglobulin free light chain assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the free light chain assay in the evaluation and management of multiple myeloma and related plasma cell disorders. In the context of screening, the serum free light chain assay in combination with serum protein electrophoresis and immunofixation yields high sensitivity, and negates the need for 24-hour urine studies for diagnoses other than light chain amyloidosis. Second, the baseline free light chains measurement is of major prognostic value in virtually every plasma cell disorder. Third, the free light chain assay allows for quantitative monitoring of patients with oligosecretory plasma cell disorders, including AL, oligosecretory myeloma, and nearly twothirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial free light chains measurements outperform protein electrophoresis and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial free light chains measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using free light chain assay in place of 24-hour urine electrophoresis for monitoring or for serial measurements in plasma cell disorders with measurable disease by serum or urine electrophoresis.

scholarly journals The Importance of Free Light Chains of Immunoglobulins Determination in Serum

2007 ◽  
Vol 26 (4) ◽  
pp. 269-273
Author(s):  
Velibor Čabarkapa ◽  
Zoran Stošić ◽  
Mirjana Đerić ◽  
Ljiljana Vučurević-Ristić ◽  
Mirjana Drljača
Keyword(s):  
Diagnostic Marker ◽  
Protein Electrophoresis ◽  
Light Chains ◽  
Malignant Diseases ◽  
Free Light Chains ◽  
Serum Free ◽  
M 12 ◽  
Serum Free Light Chains ◽  
Bence Jones Proteinuria

The Importance of Free Light Chains of Immunoglobulins Determination in SerumFor many years, Bence Jones proteinuria has been an important diagnostic marker for multiple myeloma. Relatively new serum tests for free kappa and free lambda light chains of immunoglobulins reflect the production of free light chains more accurately than urine tests. In this study, we examined the value of serum free light chains measurement in the diagnosis of some neoplastic diseases and the discrepance between the findings of serum protein electrophoresis and serum free light chains. Thirty one patients (f=19, m=12) were included in the study, most of them with blood malignant diseases. The results show that in six patients with normal gamma and beta electrophoresis fractions there are abnormal levels of free light chains and/or an abnormal κ/LD ratio. In 20 patients we found an abnormal κ/LD ratio, and in 21 patients we found an abnormal κ or LD level, or both. The obtained results show the important role of serum free light chains determination in identifying patients with monoclonal gammopathies.

Serum and Urine Protein Electrophoresis and Serum-Free Light Chain Assays in the Diagnosis and Monitoring of Monoclonal Gammopathies

2020 ◽  
Vol 5 (6) ◽  
pp. 1358-1371
Author(s):  
Gurmukh Singh
Keyword(s):  
Light Chain ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Urine Protein ◽  
Serum Free ◽  
Monoclonal Gammopathies ◽  
Serum Free Light Chain ◽  
Serum Free Light Chains

Abstract Background Laboratory methods for diagnosis and monitoring of monoclonal gammopathies have evolved to include serum and urine protein electrophoresis, immunofixation electrophoresis, capillary zone electrophoresis, and immunosubtraction, serum-free light chain assay, mass spectrometry, and newly described QUIET. Content This review presents a critical appraisal of the test methods and reporting practices for the findings generated by the tests for monoclonal gammopathies. Recommendations for desirable practices to optimize test selection and provide value-added reports are presented. The shortcomings of the serum-free light chain assay are highlighted, and new assays for measuring monoclonal serum free light chains are addressed. Summary The various assays for screening, diagnosis, and monitoring of monoclonal gammopathies should be used in an algorithmic approach to avoid unnecessary testing. Reporting of the test results should be tailored to the clinical context of each individual patient to add value. Caution is urged in the interpretation of results of serum-free light chain assay, kappa/lambda ratio, and myeloma defining conditions. The distortions in serum-free light chain assay and development of oligoclonal bands in patients‘ status post hematopoietic stem cell transplants is emphasized and the need to note the location of original monoclonal Ig is stressed. The need for developing criteria that consider the differences in the biology of kappa and lambda light chain associated lesions is stressed. A new method of measuring monoclonal serum-free light chains is introduced. Reference is also made to a newly defined entity of light chain predominant intact immunoglobulin monoclonal gammopathy. The utility of urine testing in the diagnosis and monitoring of light chain only lesions is emphasized.

Correlation Among Different Plasma Cell Disorders Markers and Immunoglobulin Heavy Light Chains (HLC)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3148-3148
Author(s):  
Ajay K. Nooka ◽  
Jonathan L. Kaufman ◽  
Nishi N Shah ◽  
Bilal Hassan ◽  
Lawrence H. Boise ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Strong Correlation ◽  
Research Funding ◽  
Light Chains ◽  
Free Light Chains ◽  
Plasma Cell Disorders ◽  
Plasma Cell Disorder ◽  
Serum Free Light Chains ◽  
M Spike ◽  
Cell Disorder

Abstract Background Heavy light chain (HLC) assays allow for accurate quantification of involved and uninvolved immunoglobulins (Ig) of the affected isotype. HLC ratio is of particular interest in measuring low level disease where there is limited utility for serum protein electrophoresis (SPEP) to measure the low M-spike and challenging to quantify. Serum immunofixation (SIFx), being a non-quantitative test cannot accurately define the amount of disease. Limited data exists to understand the utility of HLC testing, hence we tried to study the correlation of this test to some of the established plasma cell disorder markers: serum free light chains (SFLC), SPEP (M-spike) and involved total Ig levels. Methods A total of 1098 samples from 480 patients with IgG [315 IgG Kappa (k) and 165 IgG Lambda (l)] plasma cell disorders (multiple myeloma, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma and plasmacytoma) and 329 samples from 160 IgA (98 IgAk patients and 60 IgAl) plasma cell disorder patients were included in analysis. Correlation was determined between HLC levels, HLC ratio and SFLC levels for all patients. Correlation was determined for each isotype separately using non parametric Spearman Correlation co-efficient (SCC). Results In IgA patients, there is strong correlation between HLC levels (IgAk and IgAl) and M-spike (0.85; p<0.0001 and 0.82; p<0.0001, respectively) as well as involved Ig (0.99; p<0.0001; 0.99; p<0.0001, respectively). Similar strong correlation was seen between HLC ratios and M-spike and involved Ig. In IgG patients, there is strong correlation, but smaller than IgA, between HLC levels (IgGk and IgGl) and M-spike (0.72; p<0.0001 and 0.75; p<0.0001, respectively) as well as involved Ig (0.91; p<0.0001; 0.78; p<0.0001, respectively). Similar correlation was seen between HLC ratios and M-spike and involved Ig. We also observed a strong correlation of FLCk with IgAk (0.65; p<0.0001) as well as of FLCl with IgA l too (0.69; p<0.0001). Similarly, FLCk with IgGk (0.56; p<0.0001) and FLCl with IgG l (0.69; p<0.0001) exhibited strong correlation. Conclusion The presence of strong correlation between M-spike quantification, serum free light chains, as well as total involved immunoglobulins in the largest sample size reported to date, suggests the feasibility of detection of isotype bands with HLC antibodies and its potential role for clinical utility in disease staging and monitoring. Prognostic usefulness of this testing in identifying residual disease and its correlation with survival in myeloma patients will be presented at the meeting. Disclosures: Kaufman: Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Boise:Onyx Pharmaceuticals: Consultancy. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.

scholarly journals Clinical usefulness of serum free light chains measurement in patients with multiple myeloma: comparative analysis of two different tests

2017 ◽  
Vol 71 (0) ◽  
pp. 40-46
Author(s):  
Tadeusz Kubicki ◽  
Dominik Dytfeld ◽  
Aleksandra Baszczuk ◽  
Ewa Wysocka ◽  
Mieczysław Komarnicki ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Protein Electrophoresis ◽  
Light Chains ◽  
Weak Correlation ◽  
Free Light Chains ◽  
Urine Protein ◽  
Serum Free ◽  
Activity Assessment ◽  
Serum Free Light Chains ◽  
Disease Activity Assessment

<b>Introduction:</b> There are two commercially available tests for measurement of serum free light chains (sFLC) in multiple myeloma (MM) patients – Freelite and N Latex FLC. The aim of this study was to perform an assessment and direct comparison of the usefulness of the methods in routine clinical practice.<br/><b>Methods:</b> 40 refractory/relapsed MM patients underwent routine disease activity assessment studies, along with sFLC analysis using both assays. Correlation and concordance between the tests and sensitivity of studied methods of sFLC assessment were established. Special attention was focused on sFLC results in patients finally evaluated after completing the treatment. <br/><b>Results:</b> A weak correlation for the measurement of both κ [Passing–Bablok slope (PB) = 0.7681] and λ chains [(PB) = 1.542] was found. Using Bland–Altman plots, a bias of 0.0467 (κ) and -0.2133 (λ) between the measurements was documented. The concordance coefficient equaled 0.87 for κ, 0.62 for λ and 0.52 for κ/λ ratio. Ten patients had an abnormal Freelite assay κ/λ ratio and normal N Latex FLC κ/λ ratio. Three of these patients had negative serum protein electrophoresis results and fulfilled diagnostic criteria of stringent complete remission (sCR) according to N Latex FLC (but not according to Freelite). When the κ/λ ratio obtained by both methods was compared to patients’ serum/urine protein electrophoresis and immunofixation results, sensitivity of Freelite and N Latex FLC was established to be 62.5% and 41%, respectively. <br/><b>Conclusions:</b> There was no strong correlation or concordance between the two assays, and the sensitivity in terms of sFLC detection was different. This may cause problems when diagnosis of sCR is considered.

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