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.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, Chanan-Khan A, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood 2011;117:4701–5.10.1182/blood-2010-10-299529Search in Google Scholar PubMed
2. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009;23:3–9.10.1038/leu.2008.291Search in Google Scholar PubMed PubMed Central
3. Attaelmannan M, Levinson SS. Understanding and identifying monoclonal gammopathies. Clin Chem 2000;46:1230–8.10.1093/clinchem/46.8.1230Search in Google Scholar
4. Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem 2009;55:1517–22.10.1373/clinchem.2009.126664Search in Google Scholar PubMed PubMed Central
5. Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev 2009;30:105–11.Search in Google Scholar
6. Katzmann JA, Dispenzieri A. Screening algorithms for monoclonal gammopathies. Clin Chem 2008;54:1753–5.10.1373/clinchem.2008.116400Search in Google Scholar PubMed
7. Willrich MA, Katzmann JA. Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias. Clin Chem Lab Med 2016;54:907–19.10.1515/cclm-2015-0580Search in Google Scholar PubMed
8. Eisele L, Durig J, Huttmann A, Duhrsen U, Assert R, Bokhof B, et al. Prevalence and progression of monoclonal gammopathy of undetermined significance and light-chain MGUS in Germany. Ann Hematol 2012;91:243–8.10.1007/s00277-011-1293-1Search in Google Scholar PubMed
9. Basile U, Gulli F, Torti E, Napodano C, Dell’Abate MT, De Santis E, et al. Evaluation of screening method for Bence Jones protein analysis. Clin Chem Lab Med 2016;54:e331–3.10.1515/cclm-2015-1239Search in Google Scholar PubMed
10. Jenner W, Klingberg S, Tate JR, Wilgen U, Ungerer JP, Pretorius CJ. Combined light chain immunofixation to detect monoclonal gammopathy: a comparison to standard electrophoresis in serum and urine. Clin Chem Lab Med 2014;52:981–7.10.1515/cclm-2014-0023Search in Google Scholar PubMed
11. Smith JD, Raines G, Schneider HG. Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: counterpoint. Clin Chem Lab Med 2016;54:967–71.10.1515/cclm-2015-0806Search in Google Scholar PubMed
12. Fleiss JL. Measuring nominal scale agreement among many raters. Psychol Bull 1971;76:378–82.10.1037/h0031619Search in Google Scholar
13. Bakker AJ, Elderman-van der Werf C, van Abbema T. Detection and quantification of M-proteinemia: comparison of various methods for serum protein electrophoresis. Clin Chem Lab Med 2011;50:77–80.10.1515/cclm.2011.723Search in Google Scholar PubMed
14. Tate J, Caldwell G, Daly J, Gillis D, Jenkins M, Jovanovich S, et al. Recommendations for standardized reporting of protein electrophoresis in Australia and New Zealand. Ann Clin Biochem 2012;49:242–56.10.1258/acb.2011.011158Search in Google Scholar PubMed
15. Hall SL, Tate J, Gill D, Mollee P. Significance of abnormal protein bands in patients with multiple myeloma following autologous stem cell transplantation. Clin Biochem Rev 2009;30:113–8.Search in Google Scholar
16. Murray DL, Seningen JL, Dispenzieri A, Snyder MR, Kyle RA, Rajkumar SV, et al. Laboratory persistence and clinical progression of small monoclonal abnormalities. Am J Clin Pathol 2012;138:609–13.10.1309/AJCPT6OWWMHITA1YSearch in Google Scholar PubMed PubMed Central
17. Pretorius CJ. Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: point. Clin Chem Lab Med 2016;54:963–6.10.1515/cclm-2015-0699Search in Google Scholar PubMed
18. Strassle P, Hess AS, Thom KA, Harris AD. Assessing sensitivity and specificity in new diagnostic tests: the importance and challenges of study populations. Infect Control Hosp Epidemiol 2012;33:1177–8.10.1086/668036Search in Google Scholar PubMed PubMed Central
19. Kohlhagen MC, Barnidge DR, Mills JR, Stoner J, Gurtner KM, Liptac AM, et al. Screening method for M-proteins in serum using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin Chem 2016;62:1345–52.10.1373/clinchem.2015.253781Search in Google Scholar PubMed
©2018 Walter de Gruyter GmbH, Berlin/Boston
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- Frontmatter
- Editorial
- Need for better PTH assays for clinical research and patient treatment
- Reviews
- Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA
- Hair testing of GHB: an everlasting issue in forensic toxicology
- Opinion Paper
- The use of error and uncertainty methods in the medical laboratory
- Genetics and Molecular Diagnostics
- Results of the first external quality assessment scheme (EQA) for isolation and analysis of circulating tumour DNA (ctDNA)
- The importance of biochemical and genetic findings in the diagnosis of atypical Norrie disease
- General Clinical Chemistry and Laboratory Medicine
- Various glycolysis inhibitor-containing tubes for glucose measurement cannot be used interchangeably due to clinically unacceptable biases between them
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- A comparison between high resolution serum protein electrophoresis and screening immunofixation for the detection of monoclonal gammopathies in serum
- The key incident monitoring and management system – history and role in quality improvement
- Is it necessary for all samples to quantify 25OHD2 and 25OHD3 using LC-MS/MS in clinical practice?
- Contamination of dried blood spots – an underestimated risk in newborn screening
- Comparative study of the diagnostic and prognostic value of antibodies against chimeric citrullinated synthetic peptides and CCP3/CCP3.1 assays
- Development and validation of a multivariable prediction rule for detecting a severe acquired ADAMTS13 activity deficiency in patients with thrombotic microangiopathies
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- Reference Values and Biological Variations
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- Cancer Diagnostics
- Prevalence and causes of abnormal PSA recovery
- Cardiovascular Diseases
- Serum omentin-1 is a novel biomarker for predicting the functional outcome of acute ischemic stroke patients
- Letters to the Editor
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- The risk of unjustified BRCA testing after the “Angelina Jolie effect”: how can we save (laboratory) medicine from the Internet?
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- Congress Abstracts
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