A comparison between high resolution serum protein electrophoresis and screening immunofixation for the detection of monoclonal gammopathies in serum
26 Jan 2018-Clinical Chemistry and Laboratory Medicine (Clin Chem Lab Med)-Vol. 56, Iss: 2, pp 256-263
TL;DR: It is 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.
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.
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University of Ottawa1, McMaster University2, Children's Hospital of Eastern Ontario3, University of Alberta4, Sunnybrook Health Sciences Centre5, Dr. Everett Chalmers Regional Hospital6, Queen's University7, University of Saskatchewan8, University of British Columbia9, Nova Scotia Health Authority10, University of Texas MD Anderson Cancer Center11, St. Michael's Hospital12, St. John's University13, University of Toronto14, London Health Sciences Centre15, Grand River Hospital16
TL;DR: Eleven consensus recommendations along with candidate recommendations for nomenclature, protein fraction reporting, test utilization, interference handling and interpretive reporting options are presented.
27 citations
TL;DR: Currently available and commonly used methods for diagnostic protein electrophoresis, including both agarose gel and capillary zone electrophoretic techniques and total protein assessments are reviewed.
Abstract: Protein electrophoresis and immunotyping can be a useful adjunct to the standard biochemical techniques for characterizing serum and urine proteins. This paper reviews currently available and commonly used methods for diagnostic protein electrophoresis, including both agarose gel and capillary zone electrophoretic techniques and total protein assessments. Immunofixation and immunosubtraction methods for identification of immunoglobulin location and class are also presented. Practical application of quality assurance and quality control strategies in compliance with American Society of Veterinary Clinical Pathology (ASVCP) best practices are discussed. Commonly encountered serum and urine electrophoretic diagnostic patterns, including electrophoretically normal, acute-phase protein responses, polyclonal gammopathies, restricted polyclonal/oligoclonal gammopathies, paraproteinemias (monoclonal or biclonal gammopathies), and Bence-Jones proteinurias are also reviewed using relevant case material. Cases in which immunofixation electrophoresis are particularly useful are highlighted, and methodologies to more accurately quantify serum monoclonal proteins (M-proteins), monitoring tests commonly used in human medicine, are discussed.
24 citations
TL;DR: Compared to other methods for multiple myeloma diagnosis, e.g. immunofixation electrophoresis and immunonephelometry, this approach is more rapid, economical and convenient, which can be a new choice for the clinical diagnosis of Bence-Jones protein related diseases.
18 citations
TL;DR: Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy.
Abstract: Background Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. Methods We used observed treatment information for patients in the University College London Hospital’s POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. Results Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. Conclusions Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy.
17 citations
TL;DR: This review will discuss possible diagnostic laboratory testing pathways for different types of peripheral neuropathy, with the goal of minimizing costs and false-positive results while maximizing the likelihood of identifying a potentially reversible etiology.
Abstract: Peripheral neuropathy is a common neurological disorder, with high prevalence especially in the aged population. The general evaluative approach is to first identify the type of peripheral neuropathy prior to investigating for a possible underlying etiology, which is an increasingly important endeavor, as many causes of peripheral neuropathy are now recognized as treatable. To this end, laboratory testing plays an important adjunctive role to a detailed history and examination. This review will discuss possible diagnostic laboratory testing pathways for different types of peripheral neuropathy, with the goal of minimizing costs and false-positive results while maximizing the likelihood of identifying a potentially reversible etiology.
10 citations
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7,318 citations
"A comparison between high resolutio..." refers methods in this paper
...Inter-adjudicator agreement was assessed using the method of Fleiss [12] using Microsoft Excel and the Real Statistics Resource Pack software ([Release 4.3]....
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...There was good inter-adjudicator agreement for both HR SPEP (κFleiss = 0.78) and CLIF (κFleiss = 0.82) interpretations....
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...Inter-adjudicator agreement was assessed using the method of Fleiss [12] using Microsoft Excel and the Real Statistics Resource Pack software ([Release 4....
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TL;DR: A new risk stratification model is provided to specifically define high-risk patients who may benefit from novel therapeutic strategies in multiple myeloma.
Abstract: New systems have emerged for diagnosis, staging and response assessment in multiple myeloma (MM). The diagnostic and response criteria recommended are primarily derived from the International Myeloma Working Group, with certain updates and clarifications. The International Staging System is the current standard for staging of myeloma. A new risk stratification model is provided to specifically define high-risk patients who may benefit from novel therapeutic strategies. This paper provides the current criteria for diagnosis, staging, risk stratification and response assessment of MM.
991 citations
National and Kapodistrian University of Athens1, Mayo Clinic2, University of Salamanca3, Roswell Park Cancer Institute4, Bosch5, Ankara University6, Harvard University7, Heidelberg University8, University of Turin9, University of Texas MD Anderson Cancer Center10, VA Boston Healthcare System11, Icahn School of Medicine at Mount Sinai12
TL;DR: The skeletal survey remains the standard method for imaging screening, but magnetic resonance imaging frequently provides valuable diagnostic and prognostic information.
400 citations
TL;DR: The major impact of using a simplified screening panel of serum PEL plus FLC rather than PEL, IFE, and FLC is an 8% reduction in sensitivity for MGUS, 23% for POEMS (7 patients), 4% for plasmacytoma (1 patient), 1% for AL, and 0.5% for SMM.
Abstract: Background: The repertoire of serologic tests for identifying a monoclonal gammopathy includes serum and urine protein electrophoresis (PEL), serum and urine immunofixation electrophoresis (IFE), and quantitative serum free light chain (FLC). Although there are several reports on the relative diagnostic contribution of these assays, none has looked at the tests singly and in combination for the various plasma cell proliferative disorders (PCPDs).
Methods: Patients with a PCPD and all 5 assays performed within 30 days of diagnosis were included (n = 1877). The diagnoses were multiple myeloma (MM) (n = 467), smoldering multiple myeloma (SMM) (n = 191), monoclonal gammopathy of undetermined significance (MGUS) (n = 524), plasmacytoma (n = 29), extramedullary plasmacytoma (n = 10), Waldenstrom macroglobulinemia (WM) (n = 26), primary amyloidosis (AL) (n = 581), light chain deposition disease (LCDD) (n = 18), and POEMS syndrome (n = 31).
Results: Of the 1877 patients, 26 were negative in all assays. Omitting urine from the panel lost an additional 23 patients (15 MGUS, 6 AL, 1 plasmacytoma, 1 LCDD), whereas the omission of FLC lost 30 patients (6 MM, 23 AL, and 1 LCDD). The omission of serum IFE as well as urine lost an additional 58 patients (44 MGUS, 7 POEMS, 5 AL, 1 SMM, and 1 plasmacytoma).
Conclusions: The major impact of using a simplified screening panel of serum PEL plus FLC rather than PEL, IFE, and FLC is an 8% reduction in sensitivity for MGUS, 23% for POEMS (7 patients), 4% for plasmacytoma (1 patient), 1% for AL, and 0.5% for SMM. There is no diminution in sensitivity for detecting MM, macroglobulinemia, and LCDD.
277 citations
"A comparison between high resolutio..." refers background in this paper
...[4] evaluated different screening panels for the detection of different monoclonal gammopathies finding SPEP alone had a sensitivity of 79% for all monoclonal gammopathies with IFE alone improving sensitivity to 87%....
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...Also, in one previous large study of 1877 patients with monoclonal gammopathies by Katzmann et al, the sensitivity of SPEP was 79% [4, 10]....
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...[4] the sensitivity of SPEP alone for the detection of paraprotein in the high tumour burden monoclonal gammopathies was 86%....
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...The high sensitivity of HR SPEP may be because the population studied here had a large proportion of the high tumour burden monoclonal gammopathies; Multiple Myeloma and MGUS for which SPEP shows better sensitivity [4]....
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TL;DR: Routine clinical laboratory techniques recommended for use in identifying monoclonal gammopathies from serum and urine and identification of cryoglobulins and immune complexes are discussed.
Abstract: Monoclonal gammopathies reflect conditions in which abnormal amounts of immunoglobulins are produced by a clone that developed from a single pro-B germ cell. The condition may reflect a disease process or be benign. The primary purpose of this review is to emphasize routine clinical laboratory techniques that currently are recommended for use in identifying monoclonal gammopathies from serum and urine. Selection of the preferred technique and correct interpretation often is dependent on an understanding of the immunological basis and clinical sequelae associated with these conditions. For this reason, we first briefly discuss the structure, production, and nature of immunoglobulins, and then describe important features of the associated diseases. Finally, we discuss strengths and weaknesses of the techniques and make reference to current recommendations to facilitate optimal testing. We discuss in detail high-resolution electrophoresis, methods for quantifying immunoglobulins, immunofixation electrophoresis, problems associated with analysis of urine immunoglobulins, and identification of cryoglobulins and immune complexes.
115 citations