Serum Versus Urine Free Light Chains for Assessment of Monoclonal Gammopathies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5307-5307
Author(s):  
Montgomery Lobe ◽  
Donald Pasquale
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Medical Center ◽  
Statistical Significance ◽  
Serum Immunoglobulin ◽  
Light Chains ◽  
Total Serum ◽  
Free Light Chains ◽  
Monoclonal Gammopathies

Abstract Introduction Monoclonal gammopathies comprise a spectrum of disorders including Monoclonal Gammopathy of Undetermined Significant (MGUS), Smoldering Multiple Myeloma (SMM), and Active Multiple Myeloma (MM) characterized by production of monoclonal immunoglobulin heavy and/or light chains. Prior to availability of the FREELITE™ (Binding Site Ltd; Birmingham, UK) assay for measurement of immunoglobulin free light chains (FLC), laboratory monitoring of these disorders used predominantly SPEP, quantitation of immunoglobulin heavy chains (quantitative immunoglobulins), and 24 urine collection for total protein and UPEP to extrapolate production of immunoglobulin light chains. The FREELITE™ assay has up to 3-log increased sensitivity (1.5-3.0 mg/L) for detection of free light chains over standard electrophoresis (500-2,000 mg/L) and immunofixation (150-500 mg/L), and since its introduction, has been an integral tool in diagnosis and monitoring of monoclonal gammopathies. This assay detects more plasma cell disorders than SPEP, UPEP and IFE combined due to its higher sensitivity and ability to derive the ratio of affected to unaffected light chain. Measurement of urine FLC using FREELITE™ has not been integrated into standard practice due to presumed variability in FLC concentration due to changes in glomerular filtration, variability in tubular reabsorption of light chains, and lack of data regarding this use. In our practice, we routinely use random urine samples instead of 24 hour urine collections which are cumbersome and suffer from poor patient compliance. Methods: The study was approved by the Stratton VA Medical Center Institutional Review Board. As it has been our practice to obtain both random urine along with serum for FLC, we retrospectively reviewed patients diagnosed with monoclonal gammopathies and compared random urine free light chains measured by FREELITE™ to serum FLC and serum quantitative immunoglobulins. Data was analyzed for correlation using Pearson product moment correlation. P values of >0.05 were considered significant. Results: We identified 23 individuals, all male (consistent with VA population). Mean (±SD) age was 68±10 years at diagnosis, creatinine 1.3±0.5 mg/dl, and 9±6 pairs of data points per patient. Five (5) had MGUS, 5 SM, and 13 MM (2 light chain only). Results are illustrated in the Table. Normalization of urine results using concurrent serum and urine creatinine did not change the statistical significance of any of the results. Table. Correlation (p<0.05) between affected serum immunoglobulin, urine FLC, and serum FLC Serum Immunoglobulin Urine FLC Serum FLC #(%) of Patients YES YES no 2(10) YES no YES 6(29) YES YES YES 5(24) No no no 7(33) YES YES 11(48) Discussion While serum FLC is adequate in the majority of patients for monitoring monoclonal gammopathies, urine FLC correlates as well as serum FLC in about ½ of the patients. In addition, in a small number of individuals, urine FLC correlates with serum total serum immunoglobulin better than serum FLC. We feel that random urine FLC is useful for monitoring monoclonal gammopathies, and in a minority of instances, provides more accurate assessment of disease activity than serum. Disclosures No relevant conflicts of interest to declare.

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.

Biclonal Multiple Myeloma with Monoclonal Free IgG3 Heavy Chain and kappa Free Light Chains.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4768-4768
Author(s):  
Alex G. Richter ◽  
Stephen Harding ◽  
Steve Rimmer ◽  
Guy Pratt ◽  
Aarnoud Huissoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Western Blot ◽  
Heavy Chain ◽  
Light Chain ◽  
Lymphoproliferative Disorder ◽  
Plasma Cells ◽  
Light Chains ◽  
Cell Transplant ◽  
Free Light Chains ◽  
Night Sweats

Abstract Background: Heavy chain disease (HCD) is a rare lymphoproliferative disorder characterized by a monoclonal heavy chain (HC) unattached to a light chain (LC). IgGHCD or γHCD typically presents as a lymphoproliferative disorder with lymphadenopathy and hepatosplenomegaly. Myeloma has been described associated with γHCD but only with a second intact Ig paraprotein. This report describes a unique presentation of multiple myeloma with monoclonal free γ3HC and kappa free light chains. Case: A 34 year old gentleman presented with mild persistent neutropenia following two episodes of pneumonia, 18 months previously. He admitted to persistent night sweats but no other significant history. Baseline investigations revealed a mild anaemia, neutropenia and a large IgG paraprotein with no associated light chain. Bone marrow aspirate and trephine confirmed myeloma. The patient was treated with cyclophosphamide, thalidomide and dexamethasone and has had a very good partial remission. He is awaiting a sibling allogeneic peripheral blood stem cell transplant. Investigations and results: Serum Electrophoresis confirmed a large IgG paraprotein (23g/l) with no associated light chain in the serum and identified as γ3 subclass by radial immunodiffusion. Western blot showed the γ3HC was truncated with a large deletion. Markedly elevated free kappa (κ) LC (503.58 mg/l [3.30–19.4]) were found in the serum with gross skewing of the kappa/lambda ratio. Urine electrophoresis revealed separate γHC and κ LC paraproteins. Western blot of the fractionated urine protein demonstrated different sized κLC aggregates. Flow cytometry of the marrow aspirate revealed an unusual staining pattern; CD5,19,38,45+ve and CD20,22,23,34,56,138 –ve plasma cells. Cytoplasmic staining revealed 2 distinct populations of plasma cells, the first producing γ3HC and the second only free κLC. Cytogenetics and FISH analysis for 14q, p53 and c-myc abnormalities were normal. Discussion: This is the first description of a Biclonal Myeloma with separate plasma cell populations producing γ3HC and κLC paraproteins. The biclonality confirms the free HC occurs as a result of abnormal synthesis not cleavage. The clinical and immunological findings are clearly different to typical findings in both γ3HCD and Myeloma. HCD has an appalling prognosis and this case is likely to have been ‘smouldering’ for 18 months, evidenced by the 2 pneumonias and persistent night sweats. There is no lymphadenopathy or organomegaly associated with γ3HCD. The immunophenotype of the malignant plasma cells is unique. Other atypical features include frank proteinuria, with a HC in the urine, but normal renal function and no radiological or biochemical evidence of bone involvement. We propose that this unique biclonal myeloma has distinct immunological and clinical features.

High Frequency of Monoclonal Immunoglobulins Exhibiting Natural Autoantibody-Like Activity in Patients with Multiple Myeloma and Waldenström Macroglobulinemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2893-2893
Author(s):  
Peggy Lymberi ◽  
Evangelos Terpos ◽  
Aikaterini Hatzioannou ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Apostolos Balafas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Carbonic Anhydrase ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Significant Proportion ◽  
Similar Proportion ◽  
Antibody Activity ◽  
Monoclonal Gammopathies ◽  
High Incidence ◽  
Monoclonal Immunoglobulins

Abstract Abstract 2893 Serum monoclonal immunoglobulins (M-Igs) of patients with monoclonal gammopathies are known to possess antibody activity against autoantigens, bacterial antigens and haptens, but their incidence is controversial. So far, high incidence of autoantibodies (autoAb) have been demonstrated against actin, Ro/SS-A and La/SS-B for M-Igs of all three classes (IgG, IgA, IgM) and against Fc fragment of IgG and the Ii group exclusively for IgM M-Ig. Other less frequent antiboby specificities of M-Igs include anti-myosin, anti-tubulin, anti-thyroglobulin and anti-DNA. M-Igs with anti-actin activity were found to express polyreactivity, which is a property of natural autoAbs (NAbs). NAbs are germ-line encoded, occur in all species, circulate in low concentrations and belong to all Ig classes. NAbs play important immunoregulatory role and anti-F(ab')2 reactivity is crucial for the establishment of the idiotypic network. The aim of this study was to investigate the frequency of human M-Igs that exhibit NAb-like activity in patients with monoclonal gammopathies and to explore possible correlations with their clinical features. Thus, 151 M-Igs (124 of IgG class: 71IgG-kappa/53 IgG-lambda and 27 of IgA class: 16 IgA-kappa/11 IgA-lambda) from patients with symptomatic multiple myeloma (MM; n=136), asymptomatic MM (n=8) or MGUS (n=7) and 50 M-Igs from patients with Waldenström Macroglobulinemia (WM) or IgM-MGUS (43 IgM-kappa and 7 IgM-lambda), without any autoimmune diseases, were studied by an in-house ELISA for polyreactivity against six autoantigens (native DNA, actin, tubulin, myosin, carbonic anhydrase, thyroglobulin) and the non-self hapten TriNitroPhenyl (TNP). Sera were also tested for antibody activity against F(ab')2 fragment of human polyclonal IgGs. Most of these antigens are known targets of NAbs. Sera were first screened with enzyme-coupled human heavy chain antibodies (anti-G, anti-M and anti-A), and reactivity–with the exception of anti-F(ab')2–was further attributed to the M-Ig using enzyme-coupled light chain antibodies (anti-kappa and anti-lambda). A significant proportion (18.2%: 35/192 evaluated patients) of pathological sera exhibited anti-F(ab')2 activity (27 from IgG-MM, 3 from IgA-MM and 5 from WM patients). Among the total M-Igs tested, 9.5% (18/189) recognised actin, 8.7% (17/194) carbonic anhydrase, 4.6% (9/194) thyroglobulin, 3.7% (7/186) TNP, 3.5% (7/196) tubulin, 2.5% (5/193) myosin and 1.5% (3/188) DNA. M-Igs reacting with actin, carbonic anhydrase, tubulin, myosin and TNP were found to belong to all three Ig classes (IgG, IgA, and IgM). Among the IgG M-Igs tested, the most frequent reactivity was that for thyroglobulin (7.6%), while among the IgA and IgM M-Igs the highest incidence observed was for actin and carbonic anhydrase (23%, 23% and 16.6%, 15.2%, respectively). Positive IgM and IgG M-Ig had either kappa or lambda light chain in a similar proportion, while positive IgA were mostly IgA-lambda (16/18). A high percentage of positive M-Igs from MM and WM patients were polyreactive (46%), i.e., reacted with at least two panel antigens. Polyreactivity was a prominent characteristic of IgA (6/6) and IgM (9/13) but not of IgG (6/36) M-Ig. Most frequent polyreactivity profile was that for actin, carbonic anhydrase and TNP. There was no significant correlation of immune-related features of symptomatic WM (immune cytopenias, cold agglutinin disease, cryoglobulinemia) or of MM characteristics (ISS, CRAB, LDH, plasma cell infiltration) with any of the detected M-Ig specificities or their NAb-like profile. In conclusion, we report for the first time anti-carbonic anhydrase and anti-TNP activity of the M-Igs from patients with monoclonal gammopathies. We also report high incidence of anti- F(ab')2 activity in the sera of these patients as well as of polyreactive M-Igs. Our findings suggest that the M-Igs with NAb activity might reflect the expansion of a clone normally producing a NAb. To-date, it has been assumed that a naive B-cell is first driven to clonal expansion by antigenic stimulation and that subsequently, an oncogenic stimulus results in malignant transformation. Assuming that certain malignant monoclonal gammopathies arise from the proliferation of a clone normally producing a NAb which recognise F(ab')2 and hence is probably involved in the regulation of the NAbs network, it may also be postulated that this may result in deregulation of this network. Disclosures: No relevant conflicts of interest to declare.

A Review of Multiple Myeloma Patients on Dialysis Treated with High Cutoff Hemodialysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5002-5002
Author(s):  
Tiina Podymow ◽  
Ahsan Alam ◽  
Murray Vasilevsky ◽  
Roch Beauchemin ◽  
Chaim Shustik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Kidney Function ◽  
Kidney Failure ◽  
Conflicts Of Interest ◽  
Controlled Trial ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Cast Nephropathy ◽  
Serum Free Light Chains

Abstract Abstract 5002 Background: Kidney failure is a major cause of morbidity in patients with Multiple Myeloma (MM). While up to half of MM patients can be shown to have renal impairment, 10% will become dialysis dependent. The main mechanism of kidney failure is cast nephropathy, which is linked to high amounts of circulating free light chains. A proposed strategy to prevent this outcome is the use of extended high cutoff (HCO) dialysis. An ongoing randomized controlled trial is testing the Gambro HCO1100 filter. Here we report the use of another dialyzer (Bellco Phylther), which has a smaller pore size than the Gambro filter, but which may prove to be as effective and is less costly. Methods: We present three patients with symptomatic MM, elevated κ or λ serum free light chains (>500mg/L), biopsy confirmed cast nephropathy, and kidney failure (estimated GFR <15ml/min/1.73 m2) requiring dialysis. In all patients, dialysis consisted of 10 hemodiafiltration dialysis sessions in the first two weeks and three times a week thereafter using a high flux Bellco Phylther HF22SD dialyzer (Bellco, Modena, Italy). All patients received concurrent chemotherapy: bortezomib 1.3mg/m2 IV and dexamethasone 40mg po on days 1, 4, 8 and 11 of a 21 day cycle and liposomal doxorubicin at 30mg/m2 on day 4 of every cycle. Serum free light chains were determined pre- and immediately post-dialysis using a nephelometric immunoassay (FREELITE, The Binding Site, Birmingham UK). Results: We observed significant (>50%) and rapid reductions in sFLCs. These reductions were sustained at 3 months in all cases, likely because of effective anti-myeloma treatment. Two of the three patients had recovery of kidney function and remain dialysis-independent at least 6 months after cessation of dialysis. Interestingly, the only patient that did not recover kidney function was also found to have tubulointerstitial disease on renal biopsy in addition to cast nephropathy. Conclusions: The HCO Bellco Phylther dialyzer appears effective in the rapid reduction of sFLCs in light chain MM patients with cast nephropathy requiring dialysis and concurrent anti-myeloma drug therapy. While the numbers are small, our review suggests that patients with uncomplicated MM cast nephropathy may benefit from aggressive hemodiafiltration with this HCO membrane. This dialysis membrane and protocol are worth considering for further study in patients with MM cast nephropathy. Disclosures: No relevant conflicts of interest to declare.

Quantitative Assay of Immunoglobulin Free Light Chains (FLC): Evaluation of Monoclonal Versus Polyclonal Antibody and Immunoturbidimetric Versus Immunonephelometric Detection Technology

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5680-5680
Author(s):  
Dragana Segulja ◽  
Danica Matisic ◽  
Dunja Rogic ◽  
Andrea Tesija Kuna ◽  
Ines Vukasovic ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Polyclonal Antibody ◽  
Light Chain ◽  
Polyclonal Antibodies ◽  
Diagnostic Algorithm ◽  
Weighted Kappa ◽  
Light Chains ◽  
Free Light Chains ◽  
Detection Technology ◽  
Analytical Platforms

Abstract Introduction. It has been rarely reported that a laboratory test introduced so rapid and radical changes in diagnostic algorithm as is the case with the quantitative assay of free light chains of immunoglobulins (FLC) in serum and its role in the diagnostic algorithm of monoclonal gammopathies. Since the first description of immunoassay in year 2001 until today, new evidence has continuously been reported in the literature that confirm the clinical usefulness of this test in diagnosis, monitoring and prognosis of monoclonal plasma-proliferative diseases, especially diseases of light chains such as primary amyloidosis, light chain deposition disease (LCDD) or light chain multiple myeloma (LCMM) and nonsecretory multiple myeloma (NSMM). Recently, a commercial test has become available on the market that uses polyclonal antibodies to specific epitopes of free light chains which are hidden in the intact immunoglobulin molecules. In 2011, a commercial immunoassay was launched on the market that uses monoclonal instead of polyclonal antibodies, reducing the variability between different series of reagents and controlling excess antigen in the sample. Aim. The aim of this study was to evaluate monoclonal versus polyclonal antibody and immunoturbidimetric versus immunonephelometric detection technology. Does different detection tehnology – besides different used antibody – contribute to greater variability in results? Method. In this study we compared results of 40 samples measured with polyclonal antibody (The Binding Site Ltd., Birmingham, UK) and monoclonal antibody (N Latex FLC, Siemens Healthcare Diagnostics, Marburg, Germany). In other 40 samples we compared results achieved with different antibodies and different analytical platforms (Siemens Nephelometer with Roche Cobas). Results were statistically analyzed using MedCalc software. Results. Results are shown in Table 1. Comparing all results, it is evident that there is at least proportional error when comparing different antibodies and different analytical systems. Although it is known that immunoturbidimetry is less sensitive than immunonephelometric method, greater discrepancies in results were not found. When we categorized patients as positive and negative according to manufacturer's reference interval for kf/lf ratio, agreement between groups with different antibody and same detection technology was 63% (weighted kappa 0.30). Agreement between groups with different antibodies and different detection technology was 86% (weighted kappa 0.22). Although we have not measured the same samples when testing antibody and analytical platform, the selected analytical platform has, according to our results, no additional impact on the variability of results. Abstract 5680. Table 1. Comparison of FLC results using different antibody and different analytical platforms Method FLC kappa polyclonal Ab Nephelometer Siemens FLC kappa monoclonal Ab Nephelometer Siemens FLC lambda polyclonal Ab Nephelometer Siemens FLC lambda monoclonal Ab Nephelometer Siemens Results (min-max) 6.59-5210.00 6.34-1600.00 1.67-3010.00 1.00-1600.00 Passing-Bablok fit intercept (95% Cl) 8.2442.9255 to 14.9249 1.0945-1.5910 to 5.5631 slope (95% Cl) 0.5950.4564 to 0.7852 1.87981.5336 to 2.1045 Correlation rs (p<0.0001) 0.911 0.887 Method FLC kappa polyclonal Ab Cobas Roche FLC kappa monoclonal Ab Nephelometer Siemens FLC lambda polyclonal Ab Cobas Roche FLC lambda monoclonal Ab Nephelometer Siemens Results (min-max) 2.40-453.20 1.10-342.00 2.30-452.10 10.30-301.20 Passing-Bablok fit intercept (95% Cl) 2.622-3.8207 to 9.3023 0.1585-3.9731 to 4.5892 slope (95% Cl) 1.51.2972 to 1.9933 0.74160.6174 to 0.8708 Correlation rs (p<0.0001) 0.873 0.929 Conclusion. Physicians and especially clinical biochemists must be aware of the technical shortcomings of this test, such as the variability between different series (lots) reagents, non-linearity, unreliable detection of excess antigen and overestimation of FLC concentrations due to nonspecific interference or polymerization. Although initial results are not discouraging, it will be necessary to collect much more evidence, especially bearing in mind that use of monoclonal antibodies along with advantages has certain disadvantages. In the future, it will probably be necessary to incorporate into the guidelines a recommendation to report the method used, like for other tumor markers. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2900-2902 ◽  
Author(s):  
Mark Drayson ◽  
Lian X. Tang ◽  
Roger Drew ◽  
Graham P. Mead ◽  
Hugh Carr-Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Activity ◽  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Using sensitive, automated immunoassays, increased concentrations of either κ or λ free light chains (and abnormal κ/λ ratios) were detected in the sera of 19 of 28 patients with nonsecretory multiple myeloma. Four other patients had suppression of one or both light chains, and the remaining 5 sera had normal or raised free light-chain concentrations with substantially normal κ/λ ratios. Six of the patients with an elevated single free light chain, who were studied during follow-up, had changes in disease activity that were reflected by the changes in free light-chain concentrations. It is concluded that quantification of free light chains in serum should prove useful for the diagnosis and monitoring of many patients with nonsecretory myeloma.

IgD-λ multiple myeloma with excessive excretion of free light chains: a diagnostic trap in the identification of monoclonal gammopathies

2019 ◽  
Vol 77 (1) ◽  
pp. 107-111
Author(s):  
Hanane Zahir ◽  
Abdelali Tali ◽  
Meryem Rachidi ◽  
Hanane Mouhib ◽  
Hayat Daif ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chains ◽  
Free Light Chains ◽  
Monoclonal Gammopathies

scholarly journals Serum Free Light Chains: An Alternative to the Urine Bence Jones Proteins Screening Test for Monoclonal Gammopathies

2006 ◽  
Vol 52 (9) ◽  
pp. 1743-1748 ◽  
Author(s):  
Peter G Hill ◽  
Julia M Forsyth ◽  
Baldeep Rai ◽  
Stewart Mayne
Keyword(s):  
Light Chain ◽  
False Positive ◽  
False Positive Rate ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Monoclonal Gammopathies ◽  
Positive Serum ◽  
Positive Rate ◽  
Serum Free Light Chains

Abstract Background: Retrospective analyses have established the role of quantitative serum free light chains (FLCs) in the diagnosis of monoclonal light chain disorders. The aims of this study were to assess (a) whether the addition of serum FLCs to serum protein electrophoresis (SPEP) identified additional patients with monoclonal gammopathies; (b) whether serum FLC measurements could replace urinalysis for Bence Jones protein (BJP); and (c) the cost/quality implications of routinely measuring serum FLCs. Methods: Serum FLCs were added to consecutive requests for SPEP from August to November 2004 and measured by automated immunoassay. Results: Seventy-one of 923 patients had abnormal serum FLC ratios. Seven patients with monoclonal gammopathies and 1 patient with malignant lymphoma (but no monoclonal band) were detected among 43 patients with negative SPEP but positive serum FLC ratios. Thirty-five patients with negative SPEP had false-positive serum FLC ratios. The false-positive rate for a ratio &gt;1.65 was higher than previously described and associated with polyclonal increases in immunoglobulins and renal impairment. Serum FLC ratios were normal in 2 of 13 patients with low-level persistent urine BJP. However, no significant pathology would have been missed by replacing BJP with serum FLCs. Revenue and manpower savings offset 60% of the costs of serum FLCs. Conclusions: Additional diagnostic information is gained by adding serum FLCs to SPEP as first-line tests for investigating possible B-cell disorders. The quality of the diagnostic service is enhanced by more confident exclusion of light chain disorders and improved interpretive assessment of SPEP and immunofixation electrophoresis.

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