Elimination of the Need for Urine Studies during Diagnostic Studies of Monoclonal Gammopathies by the Combined Use of Serum Immunofixation and Serum Free Light Chain Assays.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5011-5011
Author(s):  
Jerry A. Katzmann ◽  
Angela Dispenzieri ◽  
Robert Kyle ◽  
Melissa R. Snyder ◽  
Mathew F. Plevak ◽  
...  
Keyword(s):  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Diagnostic Algorithm ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Urine Protein ◽  
Serum Free ◽  
Monoclonal Gammopathies ◽  
Serum Free Light Chain ◽  
Monoclonal Proteins

Abstract Due to the diagnostic sensitivity of serum free light chain quantitation for monoclonal light chain diseases, it has been suggested that urine assays no longer need be performed as part of the diagnostic algorithm for monoclonal proteins. We reviewed our experience to determine the relative diagnostic contribution of urine assays. Methods: Patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis who also had a serum immunofixation and serum free light chain quantitation within 30 days of diagnosis were identified (n = 428). The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. Results: The patients in this cohort had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. By definition of the cohort, all 428 had a monoclonal urine protein. 86% had an abnormal serum free light chain K/L ratio, 81% had an abnormal serum protein electrophoresis, and 94% had an abnormal serum immunofixation. In only 2 patients, however, were all 3 serum assays normal. Both of these were patients with monoclonal gammopathy of undetermined significance (idiopathic Bence Jones proteinuria). Conclusion: Discontinuation of urine studies and reliance on a diagnostic algorithm using solely serum studies (protein electrophoresis, immunofixation, and free light chain quantitation), missed 2 of the 428 monoclonal gammopathies (0.5 %) with urinary monoclonal proteins, and these 2 cases required no medical intervention.

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.

Serum Free Kappa to Free Lambda Ratios as an Adjunct to Serum Protein Electrophoresis for the Detection of Monoclonal Proteins in the Serum.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4856-4856
Author(s):  
Arthur R. Bradwell ◽  
Jean Garbincius ◽  
Earle W. Holmes
Keyword(s):  
Serum Protein ◽  
Light Chain ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Serum Protein Electrophoresis ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain ◽  
Monoclonal Proteins

Abstract Serum free light chain measurements have been shown to be useful in the diagnosis and monitoring of patients with monoclonal gammopathies. The present study was undertaken to evaluate the effect of adding the measurement of serum free light chain kappa to lambda ratios to the serum protein electrophoresis evaluation that we typically use as an initial screen for the detection of monoclonal proteins. We retrospectively tested 347 consecutive samples from individuals who had no previous history of plasma cell dyscrasia and had not previously had a serum or urine electrophoresis or immunofixation electrophoresis test at our institution. The quantitative serum protein electrophoresis test that was ordered was performed using Hydragel Beta 1- Beta 2 gels and Hydrasis instrument (Sebia, Inc., Norcross, GA). The protein content of the electrophoresis zones were quantitated by scanning densitometry and the electrophoresis pattern of each sample was qualitatively examined for abnormal bands and suspicious findings by a single, experienced observer. Serum free light chain concentrations and the serum free light chain kappa to lambda ratios were determined using the Freelite Human Kappa and Lambda Kits (The Binding Site Ltd, Birmingham, UK) and the Immage analyzer (Beckman Coulter Inc., Brea, CA). The serum free light chain kappa to lambda ratios were outside the reference interval (0.25 to1.65) in 23 of the samples. Ten abnormal ratios were observed among a group of 57 samples that had either positive or suspicious qualitative evaluations for the presence of a restriction or that demonstrated hypo-gammaglobulinemia. Both abnormalities led to recommendations for follow-up testing, which confirmed the presence of a monoclonal protein in 21 of the samples. Six abnormal ratios were observed among a group of 159 specimens that had quantitative abnormalities in albumin or one or more of globulin fractions (hypo-gammaglobulinemia excepted) and normal qualitative evaluations. Seven abnormal ratios were observed among a group of 131 samples that had normal quantitative results and normal qualitative evaluations. Follow-up testing is not usually recommended for serum protein electrophoresis results like those in the latter two groups. We found that the addition of the serum free light chain kappa to lambda ratio to the serum protein electrophoresis test increased the number of abnormal screens that would have required further clinical and/or laboratory evaluation by 23%(i.e. from 57 to 70). Given the high specificity of the serum free light chain kappa to lambda ratio for monoclonal light chains, the additional 13 abnormal samples identified by this test are expected to have a high likelihood of harboring a monoclonal protein that would have otherwise eluded detection. Pending a definitive prospective study, we estimate that the addition of a serum free light chain kappa to lambda ratio to the serum protein electrophoresis screen would increase the rate of detection of serum monoclonal proteins by as much as 1.6-fold.

scholarly journals Serum free light chain assay reduces the need for serum and urine immunofixation electrophoresis in the evaluation of monoclonal gammopathy

2009 ◽  
Vol 46 (5) ◽  
pp. 407-412 ◽  
Author(s):  
Richard B Fulton ◽  
Suran L Fernando
Keyword(s):  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Free Light Chain ◽  
Light Chains ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain ◽  
Immunofixation Electrophoresis ◽  
Monoclonal Proteins ◽  
Testing Algorithm

Background The potential for serum free light chain (sFLC) assay measurements to replace urine electrophoresis (uEPG) and to also diminish the need for serum immunofixation (sIFE) in the screening for monoclonal gammopathy was assessed. A testing algorithm for monoclonal protein was developed based on our data and cost analysis. Methods Data from 890 consecutive sFLC requests were retrospectively analysed. These included 549 samples for serum electrophoresis (sEPG), 447 for sIFE, and 318 for uEPG and urine immunofixation (uIFE). A total of 219 samples had sFLC, sEPG, sIFE and uEPG + uIFE performed. The ability of different test combinations to detect the presence of monoclonal proteins was compared. Results The sFLC κ/ λ ratio (FLC ratio) indicated monoclonal light chains in 12% more samples than uEPG + uIFE. The combination of sEPG and FLC ratio detected monoclonal proteins in 49% more samples than the combination of sEPG and sIFE. Furthermore, the sEPG + FLC ratio combination detected monoclonal protein in 6% more samples than were detected by the combined performance of sEPG, sIFE, uEPG and uIFE. However, non-linearity of the assay, the expense of repeat determinations due to the narrow measuring ranges, and frequent antigen excess checks were found to be limitations of the sFLC assay in this study. Conclusion The FLC ratio is a more sensitive method than uIFE in the detection of monoclonal light chains and may substantially reduce the need for onerous 24 h urine collections. Our proposed algorithm for the evaluation of monoclonal gammopathy incorporates the sFLC assay, resulting in a reduction in the performance of labour intensive sIFE and uEPG + uIFE while still increasing the detection of monoclonal proteins.

Comparison of Serum Free Light Chain Assay and Urine Protein Electrophoresis for the Detection of Monoclonal Gammopathies

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S10-S10
Author(s):  
Rongrong Huang ◽  
Xin Yi
Keyword(s):  
Positive Predictive Value ◽  
Light Chain ◽  
Predictive Value ◽  
Diagnostic Performance ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Urine Protein ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Higher Sensitivity

Abstract Laboratory detection of monoclonal immunoglobulins is essential for the diagnosis and monitoring of monoclonal gammopathies (MGs). In alignment with the recent effort from the College of American Pathologists (CAP) to develop evidence-based clinical practice guideline for laboratory detection and initial diagnosis of MGs, we retrospectively collected 1-year laboratory results from three tests, including serum protein electrophoresis (SPEP) with reflex to immunofixation (IFE), urine protein electrophoresis (UPEP) with reflex to immunofixation (IFE), and serum free light chain analysis (FLC), to identify the current ordering patterns from clinical care providers and analyze the diagnostic performances of these tests. From February 2018 to February 2019, there were a total of 5,614 SEPEs ordered with 19% reflexed for IFE. Among these, 70% were reported negative for SPEP without reflexing to IFE and 5% were reported negative after confirmation by IFE, with the rest being positive for monoclonal immunoglobulin(s) confirmed by either current or previous IFE results. Together with SPEP, FLC was ordered more often than UPEP (36% vs 19% of the total SPEP orders), with 12% of these having all three tests ordered. Using serum immunofixation results as a reference, we compared the diagnostic performance of UPEP and FLC as initial screening tools, with FLC considered abnormal if abnormal kappa/lambda ratio was accompanied with at least one elevated free light chain concentration. FLC had slightly higher sensitivity compared to UPEP (63% vs 56%) but with lower positive predictive value (69% vs 82%). When combining FLC with UPEP, the sensitivity increased to 79% with a positive predictive value of 71%. Interestingly, FLC and UPEP also showed various sensitivity in detecting specific type of free light chains, with FLC being positive in 81% of UPEP with detectable free kappa light chain, but only positive in 62% of UPEP with detectable free lambda light chain. Due to the reflex algorithm nature, those specimens with negative SPEP were not reflexed for IFE and therefore could not be used to assess the performance of FLC and UPEP. In summary, FLC was more frequently ordered than UPEP in addition to SPEP by our clinicians, although the majority of SPEPs were still ordered alone. In our practice, FLC and UPEP had comparable performance, with FLC showing slightly higher sensitivity but lower specificity. The current data did not support the replacement of one with the other, given that there was only 50% overlapping on positive identifications between FLC and UPEP. Further studies to include serum IFE for all specimens and clinical correlations would be beneficial to fully assess the diagnostic performance of FLC and UPEP, as well as their utilizations for various patient populations and clinical purpose.

scholarly journals Screening and Diagnosis of Monoclonal Gammopathies: An International Survey of Laboratory Practice

2017 ◽  
Vol 142 (4) ◽  
pp. 507-515 ◽  
Author(s):  
Jonathan R. Genzen ◽  
David L. Murray ◽  
Gyorgy Abel ◽  
Qing H. Meng ◽  
Richard J. Baltaro ◽  
...  
Keyword(s):  
Capillary Electrophoresis ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Protein Electrophoresis ◽  
Agarose Gel ◽  
Laboratory Practice ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Capillary Zone ◽  
Screening And Diagnosis

Context.— Serum tests used for the screening and diagnosis of monoclonal gammopathies include serum protein electrophoresis (SPE; agarose gel or capillary zone), immunofixation (IFE) and immunosubtraction capillary electrophoresis, serum free light chains, quantitative immunoglobulins, and heavy/light–chain combinations. Urine protein electrophoresis and urine IFE may also be used to identify Bence-Jones proteinuria. Objective.— To assess current laboratory practice for monoclonal gammopathy testing. Design.— In April 2016, a voluntary questionnaire was distributed to 923 laboratories participating in a protein electrophoresis proficiency testing survey. Results.— Seven hundred seventy-four laboratories from 38 countries and regions completed the questionnaire (83.9% response rate; 774 of 923). The majority of participants (68.6%; 520 of 758) used agarose gel electrophoresis as their SPE method, whereas 31.4% (238 of 758) used capillary zone electrophoresis. The most common test approaches used in screening were SPE with reflex to IFE/immunosubtraction capillary electrophoresis (39.3%; 299 of 760); SPE only (19.1%; 145 of 760); SPE and IFE or immunosubtraction capillary electrophoresis (13.9%; 106 of 760); and SPE with IFE, serum free light chain, and quantitative immunoglobulins (11.8%; 90 of 760). Only 39.8% (305 of 767) of laboratories offered panel testing for ordering convenience. Although SPE was used by most laboratories in diagnosing new cases of myeloma, when laboratories reported the primary test used to follow patients with monoclonal gammopathy, only 55.7% (403 of 724) chose SPE, with the next most common selections being IFE (18.9%; 137 of 724), serum free light chain (11.7%; 85 of 724), and immunosubtraction capillary electrophoresis (2.1%; 15 of 724). Conclusions.— Ordering and testing practices for the screening and diagnosis of monoclonal gammopathy vary widely across laboratories. Improving utilization management and report content, as well as recognition and development of laboratory-directed testing guidelines, may serve to enhance the clinical value of testing.

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