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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 / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Variable and inaccurate serum IgG4 levels resulting from lack of standardization in IgG subclass assay calibration

Luca Bernasconi / Esther Mundwiler / Stephan Regenass / Vincent Aubert / Angelika Hammerer-Lercher / Ingmar Heijnen
Published Online: 2019-06-11 | DOI: https://doi.org/10.1515/cclm-2019-0261

Abstract

Background

The quantification of serum IgG4 is commonly performed during the diagnostic workup of IgG4-related diseases (IgG4-RD). According to recent literature, IgG4 values above 1.35 g/L are characteristic of IgG4-RD and support its diagnosis at initial presentation. The purpose of this study was to evaluate comparability and accuracy of the two main commercially available IgG4 assays (Siemens Healthineers and The Binding Site).

Methods

Method comparison was performed for IgG and IgG subclasses using a collective of selected samples with elevated serum IgG4. In addition, we assessed the accuracy of both assays using purified polyclonal and monoclonal IgG4 preparations.

Results

Our data show significant discrepancies between the two IgG subclass assays for the measurement of IgG4 and, to a lesser extent, IgG3.

Conclusions

The lack of standardization between the two main providers of commercially available IgG4 assays leads to significant inter-assay result discrepancies, which might potentially cause unnecessary clinical workup. We conclude that serum IgG4 assay-specific decision limits, and not an assay-independent single cut-off level for IgG4 (e.g. 1.35 g/L), should be used when assessing patients for IgG4-RD. An internationally recognized, certified reference material for IgG subclasses is urgently needed, and assay manufactures are encouraged to undertake steps toward standardization of measurements of IgG4 and other IgG subclasses.

This article offers supplementary material which is provided at the end of the article.

Keywords: IgG subclasses; IgG4-related disease; IgG4 quantification; standardization

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About the article

Corresponding author: Luca Bernasconi, PhD, Institute of Laboratory Medicine, Kantonsspital Aarau AG, Tellstr. 25, 5001 Aarau, Switzerland, Phone: +41 62 838 53 15, Fax: +41 62 838 53 99


Received: 2019-03-07

Accepted: 2019-05-15

Published Online: 2019-06-11


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

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), 20190261, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2019-0261.

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