In vitro evaluation of potential interference of lokivetmab with protein electrophoresis and immunofixation

2021 ◽  
Vol 49 (04) ◽  
pp. 278-283
Author(s):  
Neoklis Apostolopoulos ◽  
Athanasia Mitropoulou ◽  
Gesine Foerster ◽  
Klaus Failing ◽  
Andreas Moritz ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Serum Protein ◽  
Monoclonal Gammopathy ◽  
Reference Interval ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Before And After ◽  
Immunofixation Electrophoresis ◽  
Therapeutic Monoclonal Antibodies

Abstract Objective In humans, misdiagnoses of monoclonal gammopathy after use of therapeutic monoclonal antibodies has been documented. This triggers concerns for similar misdiagnoses in animals treated with monoclonal antibodies. The aim of this study was to evaluate if lokivetmab interferes with serum protein electrophoresis and immunofixation electrophoresis in dogs. Material and methods Residual sera from 25 client-owned, healthy blood donor dogs from 2 veterinary hospitals in Germany were used. The residual sera were analysed with serum protein electrophoresis and immunofixation electrophoresis before and after being spiked with lokivetmab at a concentration of 10 µg/ml (corresponding to the mean peak serum concentration after a subcutaneous injection of 2 mg/kg lokivetmab). Results No monoclonal gammopathy was observed on serum protein electrophoresis and all proteins had a normal distribution pattern without any pathologic bands on immunofixation electrophoresis. The absolute γ-globulin values of spiked samples, however, were significantly higher than in the native sera although they remained within the reference interval. No other globulin fractions were significantly different. Conclusion and clinical relevance This study suggests that lokivetmab at a dose of 2 mg/kg is not detected as a monoclonal peak on serum protein electrophoresis or immunofixation electrophoresis, and thus is unlikely to lead to a misdiagnosis of other diseases that are characterised by monoclonal gammopathies.

scholarly journals Superiority of Serum Immunofixation Electrophoresis over Serum Protein Electrophoresis in the Diagnosis of Multiple Myeloma

2018 ◽  
Vol 36 (3) ◽  
pp. 95-100
Author(s):  
Mohammed Mosleh Uddin ◽  
Md Mizanur Rahman ◽  
Syeda Adib Sultana ◽  
Debashish Saha
Keyword(s):  
Multiple Myeloma ◽  
Serum Protein ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Cell Lineage ◽  
Armed Forces ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Suspected Case ◽  
Immunofixation Electrophoresis

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

Measurement of Monoclonal Immunoglobulin Protein Concentration in Serum Protein Electrophoresis: Comparison of Automated vs Manual/Human Readings

2019 ◽  
Vol 51 (3) ◽  
pp. 252-258 ◽  
Author(s):  
Alex Clavijo ◽  
Nathan Ryan ◽  
Hongyan Xu ◽  
Gurmukh Singh
Keyword(s):  
Serum Protein ◽  
Protein Concentration ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Response To Treatment ◽  
Computer Assisted ◽  
Positive Bias ◽  
Monoclonal Immunoglobulin ◽  
Monoclonal Immunoglobulins ◽  
Immunofixation Electrophoresis

Abstract Background Protein concentration of monoclonal immunoglobulin in plasma-cell myeloma/multiple myeloma provides an estimate of the tumor mass and allows for monitoring of the response to treatment. Accurate and reproducible estimates of the monoclonal immunoglobulin concentration are important for patient care. Objective To address the optimum method for estimation of the concentration of monoclonal immunoglobulins. Methods Serum protein electrophoresis and immunofixation electrophoresis were conducted by using the Helena SPIFE Touch instrument. Estimation of the protein concentration of monoclonal immunoglobulin in the gamma region by computer-assisted reading was compared with the reading by technologists and pathology residents, in 300 gels. The data were compared using t-testing and analysis of variance. Results Computer-generated readings had a consistent positive bias. The correlation coefficient of the average reading by technologists and residents with the computer generated value was 0.997. The average positive bias by the computer reading was 0.29 g per dL. The intercept on the regression analysis was 0.22 g per dL. The reading by the computer was significantly higher than each of the human-interpreted readings. The readings by the 3 human groups were not significantly different amongst them. The main reason for the higher reading by the computer was inclusion of a greater area on the anodal size of the peak on the densitometric scan. Conclusions Human- and computer-interpreted readings of the protein concentration of monoclonal immunoglobulin have a high degree of correlation. The consistent positive bias by the computer reading occurred due to inclusion of a greater area of the densitometric scan on the anodal side of the peak. We suggest that vendors should adjust such computer programs to provide readings comparable to those generated by expert humans. We recommend manual delineation of the monoclonal peaks for measuring the concentration of monoclonal immunoglobulins.

scholarly journals Usefulness of serum globulin levels for discriminating patients with monoclonal gammopathies/ paraproteinemias

Biomedicine ◽  
2021 ◽  
Vol 41 (1) ◽  
pp. 31-35
Author(s):  
Neelam M Pawar ◽  
Anupama Hegde
Keyword(s):  
Serum Protein ◽  
Total Protein ◽  
Monoclonal Gammopathy ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Serum Globulin ◽  
Protein Ratio ◽  
Monoclonal Gammopathies ◽  
Median Serum ◽  
Control Study

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.

Test Utilization of Serum Protein Electrophoresis and Immunofixation Electrophoresis

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S146-S147
Author(s):  
Roula Katerji ◽  
Tamera Paczos ◽  
Li Liu
Keyword(s):  
Multiple Myeloma ◽  
Serum Protein ◽  
Active Treatment ◽  
Cost Effective ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Efficient Test ◽  
Testing Frequency ◽  
Immunofixation Electrophoresis ◽  
Changes Over Time

Abstract Objectives Serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) are commonly used to screen and monitor monoclonal gammopathies. Currently, there are no consensus guidelines on optimal testing frequency leading to overutilization. Here we examined the testing frequencies of SPE and IFE in our institution to provide an evidence-based perspective on efficient test utilization. Methods We retrospectively reviewed all SPE and IFE tests performed in 2018. Ordering patterns and testing frequencies were analyzed. In cases with more than monthly repeats, electronic medical records were reviewed to follow the result changes over time. Results There were 10,054 SPE and 4,248 IFE orders in 2018. The 4,248 IFE cases represented 2,439 patients, among whom 104 patients (4.3%) had IFE repeated more frequently than every 2 months and 50 patients (2%) more frequently than monthly. The 10,054 SPE cases represented 5,472 patients; 127 patients (2.3%) had SPE performed more than 12 times. Rare cases (0.1%) had SPE and IFE repeated every 1 to 2 weeks. Most IFE tests were ordered together with SPE (89% of all IFE orders), among which 28% of cases had normal SPE findings. Among the cases with more than monthly SPE and IFE tests, IFE results showed meaningful interpretation changes in a minimum period of 2 to 3 months; 35% cases had no IFE interpretation changes throughout the year. In contrast, during active treatment period of multiple myeloma, SPE detected paraprotein level change weekly. Conclusion IFE is overutilized and monthly monitoring does not add value even during active treatment of multiple myeloma. Our results support the need for the development of testing frequency guidelines to avoid overutilization and provide more cost-effective patient care.

A comparison between high resolution serum protein electrophoresis and screening immunofixation for the detection of monoclonal gammopathies in serum

2018 ◽  
Vol 56 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Joel Smith ◽  
Geoffrey Raines ◽  
Hans-Gerhard Schneider
Keyword(s):  
High Resolution ◽  
Sensitivity And Specificity ◽  
Serum Protein ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Agarose Gel ◽  
Serum Free ◽  
Monoclonal Gammopathies

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.

The Detection by Immunofixation Electrophoresis (IFE) of Monoclonal Proteins in Veteran Patients with Hypogammaglobulinemia on Negative Serum Protein Electrophoresis, the Veteran Affairs Medical Center (VAMC) Experience

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S89-S89
Author(s):  
J M Petersen ◽  
M Litman ◽  
R Millili ◽  
D Jhala
Keyword(s):  
Serum Protein ◽  
Medical Center ◽  
Protein Electrophoresis ◽  
Serum Protein Electrophoresis ◽  
Time Analysis ◽  
Improvement Project ◽  
Immunofixation Electrophoresis ◽  
M Spike ◽  
Monoclonal Proteins ◽  
First Time

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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