Quantitation of serum free light chains does not compensate for serum immunofixation only when screening for monoclonal gammopathies
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Klas Böer
Abstract
Background: Detection of plasma cell dyscrasias (PCD) requires screening of serum and urine for monoclonal proteins. Several studies have demonstrated increased sensitivity and specificity when measurement of serum free light chain (SFLC) is part of the screening protocol. In addition, omission of immunofixation (IFE) in the standard work-up that includes SFLC assay has been proposed. This study attempts to define the role of the SFLC assay in a screening strategy limited to serum only. It compares outcomes to a serum-only screening strategy that omits serum IFE.
Methods: Serum from 691 patients was analysed for the presence of monoclonal protein using standard serum IFE, serum protein electrophoresis (SPE) and measurement of SFLC. Data were analysed retrospectively.
Results: Specificity and sensitivity of abnormal SFLC-ratios for the detection of monoclonal protein using IFE were 96% and 41%, respectively. Eighteen patients with negative monospecific and Bence Jones IFE, but abnormal SFLC-ratios were identified. In most cases, this could be attributed to kidney and inflammatory disease or haematological disorders. In four cases, this resulted in further diagnostic investigation and light chain disease was later detected in two cases. Light chain disease was confirmed in one case but not confirmed in the other patient. In 14 patients, Bence Jones IFE was negative, although the concentrations of SFLC suggested the presence of monoclonal Bence Jones protein at concentrations detectable by IFE. Thus, either the anti-serum failed at detection, there was polymerisation of the free light chains or the SFLC assay overestimated protein concentrations. Simulating a work-up that included IFE only if abnormalities were detected by SPE or the SFLC assay would have resulted in 26% fewer IFEs being performed, but three patients with monoclonal proteins by IFE would have been missed.
Conclusions: Abnormal SFLC concentrations are neither sensitive nor specific for the detection of monoclonal proteins by IFE. Not all PCD are accompanied by excessive production of SFLC, and several other conditions, such as renal disease are associated with increased SFLC concentrations. An abnormal SFLC-ratio is a specific marker for PCD, and occurs primarily in patients with haematological disease. If renal and inflammatory diseases are excluded, this should prompt further diagnostic investigation. Screening of serum without performing an IFE as a standard procedure leads to a reduction of sensitivity when compared to screening of serum that includes IFE.
Clin Chem Lab Med 2009;47:1109–15.
©2009 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- Editorials
- Estimating glomerular filtration rate
- Serum-free light chain analysis: works in progress
- Review
- Glomerular filtration rate measurement and prediction equations
- Genetics and Molecular Diagnostics
- Leptin gene (TTTC)n microsatellite polymorphism in pre-eclampsia and HELLP syndrome
- TaqIB polymorphism in cholesterol ester transfer protein (CETP) gene predicts future cardiovascular death in patients experiencing an acute coronary syndrome
- Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and risk for pediatric obesity
- Application of pyrosequencing to the identification of sequence variations in the cystic fibrosis transmembrane conductance regulator gene
- General Clinical Chemistry and Laboratory Medicine
- Relationship of serum bilirubin concentrations to kidney function and albuminuria in the United States adult population. Findings from the National Health and Nutrition Examination Survey 2001–2006
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- Cancer Diagnostics
- Serum free light chains: diagnostic and prognostic value in multiple myeloma
- Quantitation of serum free light chains does not compensate for serum immunofixation only when screening for monoclonal gammopathies
- Serum HER-2 concentrations for monitoring women with breast cancer in a routine oncology setting
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- Pre-treatment serum and plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in gastric cancer patients
- Infectious Disease
- Diagnosis of infection with human herpes viruses in routine laboratory practice
- Isolation and expression of UB05, a Plasmodium falciparum antigen recognised by antibodies from semi-immune adults in a high transmission endemic area of the Cameroonian rainforest
- Letters to the Editor
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- Congress Abstracts
- Congress of Clinical Chemistry and Laboratory Medicine. 6th Annual Conference of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL), Leipzig, Germany, October 7–10, 2009
- 8th Panhellenic Clinical Chemistry Congress, Patras, Greece, October 2–4, 2009
