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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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IMPACT FACTOR 2016: 3.432

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1437-4331
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In This Section
Volume 48, Issue 10 (Oct 2010)

Issues

Detection of serum free light chains: the problem with antigen excess

Markus Bosmann
  • Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
  • Laboratory Medicine, Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Germany
  • M. Bosmann and J. Kößler contributed equally to this work.
/ Jürgen Kößler
  • Laboratory Medicine, Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Germany
  • M. Bosmann and J. Kößler contributed equally to this work.
/ Herbert Stolz
  • Laboratory Medicine, Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Germany
/ Ulrich Walter
  • Laboratory Medicine, Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Germany
/ Stefan Knop
  • Division of Hematology and Medical Oncology, Department of Internal Medicine II, University Hospital Wuerzburg, Germany
/ Udo Steigerwald
  • Laboratory Medicine, Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Germany
Published Online: 2010-07-14 | DOI: https://doi.org/10.1515/CCLM.2010.283

Abstract

Background: In recent years, measurement of serum immunoglobulin free light chains (FLCs) has greatly facilitated diagnosis and monitoring of various plasma cells dyscrasias, including multiple myeloma. Detection of FLCs by nephelometry depends on the formation of immune complexes. However, it is known that if the antigen (free light chain) is present in great excess, non-precipitating immune complexes can be formed and be detected poorly. This may lead to inaccurate test results.

Methods: Serum samples from 91 patients were subjected prospectively to the detection of free κ and λ light chains by automated nephelometry. A standard dilution of 1:100 was paralleled by a 1:2000 dilution. In addition, samples with values below the effective range (1:100) were subjected to a 1:20 dilution in order to calculate the κ/λ ratio.

Results: Here, we report the incidence of antigen excess in a cohort of 91 patients with a high proportion of monoclonal abnormalities. A standard dilution (1:100) of free light κ chains from a patient with monoclonal immunoglobulin A κ gammopathy were missed repeatedly. In a second patient (with myeloproliferative disease and an apparent incidental FLC monoclonal gammopathy of undetermined significance) free λ chains were also substantially underestimated in the standard dilution. Hence, the incidence of erroneously low test results due to antigen excess was 2.20%.

Conclusions: We found a significantly higher incidence of falsely low test results due to antigen excess than reported previously. Antigen excess may result in erroneous interpretations in sera subjected to nephelometric analysis. Therefore, clinical decisions should not be based solely on a single assay, especially if FLC testing includes only one dilution of the serum sample. Instead, several parallel dilutions should be recommended for screening of patients.

Clin Chem Lab Med 2010;48:1419–22.

Keywords: antigen excess; hook effect; multiple myeloma; nephelometry; serum free light chains

About the article

Corresponding author: Markus Bosmann, MD, Department of Pathology, University of Michigan Medical School, Room 7526, MSRBI, Box 5602, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5602, USA Phone: +734 647 2929, Fax: +734 764 4308,


Received: 2010-02-04

Accepted: 2010-04-21

Published Online: 2010-07-14

Published in Print: 2010-10-01



Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2010.283. Export Citation

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