Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
-
Carel J. Pretorius
Abstract
The reliable detection of paraprotein in serum and urine is the primary purpose of electrophoretic procedures in clinical laboratories. Screening immunofixation electrophoresis (sIFE) employs a single application of antisera directed against heavy and light chains that facilitates the detection of paraproteins that migrate in the non-γ region or that are below the detection limit of protein electrophoresis. These paraproteins that are missed by routine electrophoresis occur in up to 27.3% of newly investigated and 13.6% of monitored patients. Small paraproteins missed by conventional electrophoretic techniques are clinically important in the diagnosis and monitoring of malignant plasma and B-cell disorders. The superior diagnostic performance of sIFE makes it suitable as the initial laboratory procedure to investigate paraproteins in complex serum and urine matrices.
References
1. Eisele L, Dürig J, Hüttmann A, Dührsen U, Assert R, Bokhof B, et al., on behalf of the Heinz Nixdorf Recall study investigative group. 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
2. Jenner W, Klingberg S, Tate JR, Wlgen 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
3. Tate JR, Caldwell G, Daly J, Gillis D, Jenkins M, Jovanovich S, et al., on behalf of the working party on standardised reporting of protein electrophoresis. 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
4. Cook L, Macdonald DH. Management of paraproteinaemia. Postgrad Med J 2007;83:217–23.10.1136/pgmj.2006.054627Search in Google Scholar PubMed PubMed Central
5. Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance. Br J Haematol 2006;134:573–89.10.1111/j.1365-2141.2006.06235.xSearch in Google Scholar PubMed
6. Kyle RA, Therneau TM, Rajkumar V, Larson MS, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. New Engl J Med 2006;354:1362–9.10.1056/NEJMoa054494Search in Google Scholar PubMed
7. Cancer Research UK website. http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma/incidence. Last accessed 14 July 2015.Search in Google Scholar
8. Cancer Australia website. http://canceraustralia.gov.au/affected-cancer/cancer-types/myeloma/myeloma-statistics. Last accessed 14 July 2015.Search in Google Scholar
9. National Cancer Institute, Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/statfacts/html/mulmy.html. Last accessed 14 July 2015.Search in Google Scholar
10. Bergon E, Miravalles E. Retrospective study of monoclonal gammopathies detected in the clinical laboratory of a Spanish Healthcare district: 14-year series. Clin Chem Lab Med 2007;45:190–6.10.1515/CCLM.2007.029Search in Google Scholar PubMed
11. Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009;113:5412–7.10.1182/blood-2008-12-194241Search in Google Scholar PubMed PubMed Central
12. Kyle RA, Durie BG, Landgren O, Blade J, Merlini G, Kroger N, et al., on behalf of the International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 2010;24:1121–7.10.1038/leu.2010.60Search in Google Scholar PubMed PubMed Central
13. Murray DL, Seningen JL, Dispenzieri A, Snyder MR, Kyle RA, Rajkumar SV, et al. Laboratory persistence and clinical progression of small monoclonal monoclonal abnormalities. Am J Clin Pathol 2012;138:609–13.10.1309/AJCPT6OWWMHITA1YSearch in Google Scholar PubMed PubMed Central
14. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos M, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538–48.10.1016/S1470-2045(14)70442-5Search in Google Scholar
15. Keren DF, Alexanian R, Goeken JA, Gorevic PD, Kyler RA, Tomar RH. Guidelines for the clinical and laboratory evaluation of patients with monoclonal gammopathies. Arch Path Lab Med 1999;123:106–7.10.5858/1999-123-0106-GFCALESearch in Google Scholar PubMed
16. Mateos M, Hernandez M, Giraldo P, de la Rubia X, de Arriba F, Corral LL, et al. Lenalidomide plus dexamethasone for high risk smouldering multiple myeloma. New Engl J Med 2013;369:438–47.10.1056/NEJMoa1300439Search in Google Scholar PubMed
17. Rang M. The Ulysses syndrome. Can Med Assoc J 1972;106:122–3.Search in Google Scholar
18. Durie BG, Harousseau J-L, Miguel JS, Blade J, Barlogie B, Anderson K, et al., on behalf of the International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467–73.10.1038/sj.leu.2404284Search in Google Scholar PubMed
19. Cejka J, Kithier K. IgD myeloma protein with unreactive light chain determinants. Clin Chem 1979;25:1495–8.10.1093/clinchem/25.8.1495Search in Google Scholar
©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Editorial
- Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
- Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
- Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
- Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
- Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
- The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
- Serum and Urine Protein Electrophoresis and Immunofixation Testing
- Challenges of measuring monoclonal proteins in serum
- Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
- Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
- Moving towards harmonized reporting of serum and urine protein electrophoresis
- Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
- Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
- New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
- Serum Free Light Chain Methods and Controversies
- Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
- Measurement of free light chains with assays based on monoclonal antibodies
- Measurement of free light chains – pros and cons of current methods
- Is accuracy of serum free light chain measurement achievable?
- Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
- A patient with AL amyloidosis with negative free light chain results
- Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
- Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
- New Laboratory Assays and Challenges
- Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
- Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
- Free light chains and heavy/light chains in monitoring POEMS patients
- Monitoring free light chains in serum using mass spectrometry
- Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
- Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
- Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
- Letter to the Editor
- Discrepancy between FLC assays: only a problem of quantification?
Articles in the same Issue
- Frontmatter
- Editorial
- Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
- Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
- Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
- Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
- Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
- The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
- Serum and Urine Protein Electrophoresis and Immunofixation Testing
- Challenges of measuring monoclonal proteins in serum
- Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
- Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
- Moving towards harmonized reporting of serum and urine protein electrophoresis
- Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
- Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
- New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
- Serum Free Light Chain Methods and Controversies
- Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
- Measurement of free light chains with assays based on monoclonal antibodies
- Measurement of free light chains – pros and cons of current methods
- Is accuracy of serum free light chain measurement achievable?
- Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
- A patient with AL amyloidosis with negative free light chain results
- Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
- Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
- New Laboratory Assays and Challenges
- Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
- Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
- Free light chains and heavy/light chains in monitoring POEMS patients
- Monitoring free light chains in serum using mass spectrometry
- Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
- Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
- Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
- Letter to the Editor
- Discrepancy between FLC assays: only a problem of quantification?
