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Licensed Unlicensed Requires Authentication Published by De Gruyter July 4, 2022

Serum free light chain analysis: persisting limitations with new kids on the block

  • Lieve Van Hoovels ORCID logo EMAIL logo , Martine Vercammen EMAIL logo , Louis Nevejan ORCID logo , Margot Cornette , Pieter-Jan Briers , Dries Deeren , Jan Van Droogenbroeck , Karel Fostier and Dieter De Smet EMAIL logo

Abstract

Objectives

Serum free light chain (sFLC) measurements have inherent analytical limitations impacting sFLC clinical interpretation. We evaluated analytical and diagnostic performance of three polyclonal sFLC assays on four analytical platforms.

Methods

sFLC concentration was measured using Diazyme FLC assays (Diazyme) on cobas c501/c503 analyzer (Roche); Freelite assays (The Binding Site) on Optilite analyzer (The Binding Site) and cobas c501 analyzer and Sebia FLC ELISA assays (Sebia) on AP22 ELITE analyzer (DAS). Imprecision, linearity, method comparison vs. Freelite/Optilite, antigen excess detection and reference value verification were assessed. Diagnostic performance was compared on 120 serum samples and on follow-up samples of five patients with κ and λ monoclonal gammopathy.

Results

Method comparison showed excellent correlation with Freelite/Optilite method for all assays. A large proportional negative bias was shown for both Sebia κ and λ ELISA and a significant positive proportional bias for λ in the low (<10 mg/L) Freelite/cobas c501 method. Clinically relevant underestimation of κ sFLC levels due to antigen excess was shown for 7% of each Diazyme/cobas application and for 11 and 32.1% of λ sFLC assay of respectively Diazyme/cobas and Sebia/AP22. sFLC reference values revealed application specific. Cohen’s κ values were (very) good for κ sFLC but only moderate to good for λ sFLC. In 4/10 follow-up patients, significant differences in clinical interpretation between sFLC assays were noticed.

Conclusions

Important analytical limitations remain for all sFLC applications. Differences in reference values and diagnostic performance hamper interchangeability of sFLC assays. Assay specific sFLC decision guidelines are warranted.


Corresponding authors: Lieve Van Hoovels, Department of Laboratory Medicine, OLV Hospital Aalst, Moorselbaan 164, 9300 Aalst Aalst, Belgium; and Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium, E-mail: ; Martine Vercammen, Department of Laboratory Medicine, AZ Sint-Jan Hospital Brugge – Oostende AV, Ruddershove 10, 8000 Brugge Bruges, Belgium; and Research group REIM, Vrije Universiteit Brussel (VUB), Brussels, Belgium, E-mail: ; and Dieter De Smet, Department of Laboratory Medicine, AZ Delta Hospital, Deltalaan 1, 8800 Roeselare, Belgium, E-mail:
Lieve Van Hoovels and Martine Vercammen share first authorship.

Acknowledgments

We gratefully thank manufacturers The Binding Site, Roche and Sebia for in-kind providing reagents for this study.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: The local Institutional Review Board gave ethical approval for this study.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0347).


Received: 2022-04-11
Accepted: 2022-06-21
Published Online: 2022-07-04
Published in Print: 2022-08-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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