scholarly journals Immunoglobulin Pattern in Monoclonal Gammopathy Disorders

2020 ◽  
Vol 14 (2) ◽  
pp. 160-163
Author(s):  
Monwar Tarek ◽  
Latifa Rahman ◽  
Susane Giti ◽  
Md Abdul Wahab

Introduction: The presence of abnormal monoclonal proteins, the M band, is a frequent characteristic feature of plasma cell dyscrasias and is usually detected as a discrete band in the γ or β region in serum or urine protein electrophoresis. It is characterized and confirmed by immunofixation electrophoresis (IFE). Accurate detection and quantification of monoclonal immunoglobulins are important for the diagnosis and management of monoclonal gammopathies. Objectives: To find out the pattern of immunoglobulin in monoclonal gammopathy cases and evaluate the role of IFE in the detection of them. Materials and Methods: This cross-sectional descriptive study was conducted in the Department of Haematology, Armed Forces Institute of Pathology (AFIP), Dhaka from July 2015 to December 2015. Thirty diagnosed cases of monoclonal gammopathies of both sexes were selected. Bone marrow examination, serum protein electrophoresis, skeletal survey, relevant biochemical test and IFE were performed for all the cases. Results: Out of 30 monoclonal gammopathy cases, M band was identified in 24(80%) cases by serum protein electrophoresis but by the IFE M band was found in all 30(100%) cases. Among the M band pattern of immunoglobulin was characterized by IFE and the result was; 15(50%) cases IgG Kappa, 09(30%) cases IgG Lambda, 02(6.7%) cases IgA Kappa, 02(6.7%) cases IgM Kappa and 02(6.7%) cases light chain kappa monoclonal protein. Conclusion: Though the number of the patient was limited, it is evident that in 20% gammopathy cases M band was missing by conventional serum protein electrophoresis but IFE could identify M band in all the cases. It is recommended that IFE should be carried out in all monoclonal gammopathy patients. Journal of Armed Forces Medical College Bangladesh Vol.14 (2) 2018: 160-163

Biomedicine ◽  
2021 ◽  
Vol 41 (1) ◽  
pp. 31-35
Author(s):  
Neelam M Pawar ◽  
Anupama Hegde

Introduction and Aim: The confirmatory step in diagnosis of monoclonal gammopathies is bone marrow biopsy and presence of M-protein in serum protein electrophoresis. These tests are relatively expensive & invasive for screening and unavailable in low resource settings. Increased levels of serum globulin are clue to the diagnosis of monoclonal gammopathy. The aim of this study was to assess the relevance of serum globulin levels in discriminating between patients with & without monoclonal gammopathies/ paraproteinemia. Materials and Methods: We retrospectively reviewed serum protein electrophoresis (SPE) and related investigations of patients suspected of monoclonal gammopathy. Reports with an M-band were considered as paraproteinemias, and those without as controls. ROC for sensitivities & specificities for serum globulin levels were computed. Results: For the case-control study, median serum globulin values in cases were 4.4 (3.5-6.3) g/dL in males and 3.65 (3.33-5.0) g/dL in females. They were significantly higher than those with normal SPE pattern, with a p <0.001. A cut-off value of 3.25 g/dL of globulin could distinguish between paraproteinemias and controls with a sensitivity of 82.1% and specificity of 85.4% in males; a sensitivity of 79.2%, a specificity of 76.7% for females. At a cut-off value of 3.4 g/dL, sensitivity was 77% and specificity 92.7% for males; sensitivity was 75% and specificity 83.7% for females. Alternatively, a cut-off value of 0.458 of globulin/total protein ratio could distinguish at a best sensitivity & specificity of 80% and 89% in males; 83.3% and 83.7% in females. Conclusion: Serum globulin values and globulin/total protein ratio can reliably differentiate patients with paraproteinemias.


2018 ◽  
Vol 56 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Joel Smith ◽  
Geoffrey Raines ◽  
Hans-Gerhard Schneider

Abstract Background: There are a variety of initial laboratory tests or combinations of tests that can be performed when a monoclonal gammopathy is suspected including serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation (IFE) and serum free light chain assays. Some groups have recently used simplified “screening” IFE methods for the detection of monoclonal gammopathies leveraging the greater sensitivity of IFE over SPEP alone to improve the detection of monoclonal gammopathies. These screening techniques have been predominantly evaluated against lower resolution agarose gel electrophoresis techniques. Methods: In this study we evaluated the diagnostic performance of the combined κ and λ light chain screening immunofixation (CLIF) in comparison to serum protein electrophoresis on a high-resolution (Sebia Hydragel 15 HR) agarose gel system. Each gel was interpreted by three adjudicators. A total of 156 patient samples were analysed. Adjudicated diagnoses based on the screening techniques were compared against the results of high resolution serum protein electrophoresis and high resolution standard immunofixation performed during routine laboratory operation. Where standard immunofixation was not performed a combination of a review of medical records, serum free light chains, UPEP and bone marrow aspirate and trephine and subsequent standard immunofixation and protein electrophoresis results where available were used to confirm the absence of a monoclonal gammopathy. Results: In this cohort a total of 65 (41%) patients had a paraprotein confirmed by standard immunofixation. HR SPEP had a sensitivity and specificity of 95% and 85%, respectively, while CLIF had a sensitivity and specificity of 88% and 97%, respectively. Conclusions: Overall we found that high-resolution gel serum protein electrophoresis using a Sebia Hydragel 15 HR system was more sensitive than a screening immunofixation method (CLIF) for the detection of paraproteins in patient serum in this patient cohort. The drawback of the greater sensitivity of HR SPEP was a higher false positive rate requiring an increased utilisation of follow up immunofixation electrophoresis.


2018 ◽  
Vol 36 (3) ◽  
pp. 95-100
Author(s):  
Mohammed Mosleh Uddin ◽  
Md Mizanur Rahman ◽  
Syeda Adib Sultana ◽  
Debashish Saha

Background: Multiple Myeloma (MM) is a neoplasm of B cell lineage characterized by excessive proliferation of abnormal plasma cells, secreting abnormal immunoglobulin causing monoclonal gammopathy which can be detected by the presence of M protein in serum and urine electrophoresis.Aim: Present study is aimed to detect and quantify monoclonal gamma globulins by SPEP and IFE in suspected case of MM and other plasma cell dyscrasias and also to find out the discrepant findings between SPEP and IFE.Methods: A retrospective observational study was carried out on clinically highly suspected cases of Multiple Myeloma (MM) presenting with backache, asthenia and generalized weakness at Armed forces Institute of Pathology(AFIP), Dhaka cantonment from January 2015 to July 2016. A total of 140 blood samples were collected and subjected to serum protein electrophoresis (SPEP) and Immunofixation electrophoresis (IFE). IFE identifies the type of heavy (IgG, IgM or IgA) and light chain (either kappa or lambda in suspected cases of MMResults: Out of 140 cases, SPEP identified monoclonal band in 62 cases and either non-specific findings or polyclonal band in 78 cases. At the same time immunofixation electrophoresis (IFE) which was done on all samples detected another 14 cases of M-band in addition to earlier 62 cases of monoclonal gammopathy by SPEP. Among 140 cases, SPEP detected M-band in 62 cases, whereas IFE identified monoclonal band in 76 cases. So in the remaining 14 cases (10%) small sharp spikes of monoclonal band was found only by IFE whereas SPEP failed to detect those 14 cases.Conclusion: SPEP is an easy to perform laboratory test which can be used for detection and quantification of monoclonal gammopathy but there is some limitation in detecting monoclonal band by SPEP. IFE is more sensitive to detect the monoclonal band than SPEP. So both SPEP and IFE should be done simultaneously for precise diagnosis of MM and related disorders.J Bangladesh Coll Phys Surg 2018; 36(3): 95-100


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1803-1803
Author(s):  
Melissa Snyder ◽  
Angela Dispenzieri ◽  
S.Vincent Rajkumar ◽  
Robert Kyle ◽  
Joanne Benson ◽  
...  

Abstract Abstract 1803 Poster Board I-829 Background Plasma cell proliferative disorders are monitored by a variety of methods. Serum protein electrophoresis (SPEP) and/or urine PEP M-spike quantitation are commonly assessed in patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM) to determine disease progression, response, or relapse. Serum immunoglobin (Ig) concentrations can be quantitated when the M-spike is large or if the migration is obscured within the SPEP beta fraction. Serum FLC quantitation provides a rapid indicator of response, will detect the rare occurrence of FLC escape, and will allow disease monitoring in the absence of a measurable serum or urine M-spike. The International Myeloma Working Group (IMWG) has recommended that the serum and urine M-spike should be used to monitor disease, and that FLC quantitation should be used only if there is no measurable disease by electrophoresis and if the monoclonal FLC concentration is greater than 10 mg/dL in the context of an abnormal FLC K/L ratio. We have studied serial samples in clinically stable patients in order to assess the total variability (analytic and biologic) of these assays and to confirm the IMWG recent recommendations. Methods Serial data from stable MGUS patients (n=35) were identified by the availability of all 3 serum test results (M-spike, Ig, FLC) in at least 4 serial samples that were obtained 9 months to 5 years apart and whose serum M-spikes varied by less than 25%. For MM (n=60) and SMM (n=48) the samples were within 9-15 months and serum M-spikes varied by less than 0.5 g/dL. Among the 60 MM, 48 SMM, and 35 MGUS patients, there were 23, 41, and 18 patients with measurable disease by serum M-spike (i.e. M-spike >1 g/dL); 19, 10, and 10 patients with an evaluable FLC (i.e. monoclonal FLC > 10 mg/dL and an abnormal FLC ratio); and 5, 5, and 1 patient with an evaluable urine (i.e. M-spike > 200mg/24 hr). The FLC data was analyzed as the involved FLC concentration (iFLC), the difference between the involved and uninvolved FLC concentration (dFLC), and the FLC K/L ratio (rFLC). The coefficients of variability (CV) were determined for each methodology in each patient sample set, and the average CVs were determined. Igs were quantitated by immunonephelometry using a Siemens BNII and Siemens reagent sets; kappa and lambda FLC were quantitated using a Siemens BNII and Freelite reagent sets from The Binding Site; M-spikes were quantitated using Helena SPIFE SPE and reagent sets. Results The CVs for the Ig quantitation, SPEP M-spike, FLC quantitation, and urine M-spike in each of the patient groups are listed in the table: Our laboratory's interassay analytic CV for replicate samples are 4-5% for Ig quantitation, 6-8% for SPEP M-spikes, 6-7% for FLC quantitation, and 5-7% for urine M-spikes. The analytic CVs of the methods are similar, but the total (analytic + biologic) CVs are very different. The samples have been selected by restricting the variability of serum M-spike values; when we apply the same criteria to the IgG quantitation, the IgG total CV comes closer to the serum M-spike CVs. The remaining differences, however, may be due to biologic variability contributed by polyclonal Ig. The total CV for iFLC is similar to the urine M-spike CV and suggests a previously unrecognized large biologic CV for serum FLC. The iFLC and dFLC CVs were comparable but were smaller than the rFLC CV. Conclusion The variability of the serum and urine M-spike, Ig, and FLC measurements confirm the IMWG recommendations for patient monitoring. If a patient has a measurable M-spike >1 g/dL, then the serum M-spike should be followed. If there is no measurable disease, then the iFLC can be monitored, provided that the rFLC is abnormal and the iFLC concentration is >10 mg/dL. Although the number of patients with evaluable urine M-spikes in this study is small, larger studies may confirm the utility of serum FLC compared to urine M-spike for monitoring patients with monoclonal gammopathies. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4856-4856
Author(s):  
Arthur R. Bradwell ◽  
Jean Garbincius ◽  
Earle W. Holmes

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.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5011-5011
Author(s):  
Jerry A. Katzmann ◽  
Angela Dispenzieri ◽  
Robert Kyle ◽  
Melissa R. Snyder ◽  
Mathew F. Plevak ◽  
...  

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.


2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S89-S89
Author(s):  
J M Petersen ◽  
M Litman ◽  
R Millili ◽  
D Jhala

Abstract Introduction/Objective Serum protein electrophoresis (SPEP) is the backbone laboratory test for the detection of abnormal monoclonal proteins. However, IFE is a sensitive assay that can sometimes detect monoclonal proteins even when the corresponding SPEP is negative. The fact that IFE is more sensitive than SPEP combined with the need to avoid overutilization of IFE has led to published algorithms for guidance. Hypogammaglobulinemia in a new patient has been recognized in these algorithms as a reason to reflex to IFE when SPEP is negative, though studies on veteran patients are sparse. Therefore, this QA study of the percentage of positive IFEs in negative new SPEP veteran patients with hypogammaglobulinemia was undertaken to ensure reflex IFEs would still be indicated. Methods As part of a quality assurance/quality improvement project, a retrospective Vista/Fileman search of all SPEPs with IFE performed from January 2017 to February 2019 was undertaken to identify cases of SPEPs showing hypogammaglobulinemia (&lt;0.7 g/dL). Diagnostic comments were then analyzed to identify cases of hypogammaglobulinemia along with the M-spike (&lt;0.1 g/dL) to identify negative SPEPs. Only those cases that were consistent with first time hypogammaglobulinemia without an obvious M-spike were included and tabulated for calculations. Any result that was not negative for a monoclonal band was considered as positive. Results There were a total of 194 specimens that met the criteria of SPEP with hypogammaglobulinemia and standard comments consistent with first time analysis and without an obvious M-spike on SPEP. Out of these 194 specimens, 45 had a positive result, either as a monoclonal band comigrating with the beta protein peak or as a very faint gamma or beta monoclonal band. This represented approximately 23% of the specimens, about double the literature published rate for the non-veteran population. Conclusion The performance of IFE on new hypogammaglobulinemia veteran patients appears to be indicated like previously published algorithms and is supported by the fact that about double (23%), compared to the non-veteran population, had positive IFEs despite negative SPEPs. IFE is a helpful tool for new hypogammaglobulinemia patients for the detection of monoclonal proteins despite negative SPEPs.


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