Lack of comparability of immunoassays for rheumatoid factor isotypes

Maria Infantino; Boaz Palterer; Silvia Pancani; Maurizio Benucci; Valentina Grossi; Mariangela Manfredi; Nicola Bizzaro

doi:10.1515/cclm-2023-0109

Article

Lack of comparability of immunoassays for rheumatoid factor isotypes

Maria Infantino , Boaz Palterer , Silvia Pancani , Maurizio Benucci , Valentina Grossi , Mariangela Manfredi and Nicola Bizzaro

Published/Copyright: April 7, 2023

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 9

Abstract

Objectives

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by the presence of autoantibodies that are used for classification of the disease. Though routine diagnostics is commonly restricted to measuring rheumatoid factor (RF) and anti-citrullinated protein antibodies, detection of RF IgM, IgG and IgA isotypes, may increase the power of RA serodiagnosis by reducing the number of seronegative patients as well as provide prognostic information. The agglutination-based RF assays, such as nephelometry or turbidimetry, are unable to differentiate isotypes. We compared three different immunoassays used in current laboratory practice to detect RF isotypes.

Methods

We tested 117 consecutive serum samples that were positive for total RF at nephelometry, from 55 RA and 62 non-RA subjects. IgA, IgG, and IgM isotypes of RF were tested by immunoenzymatic (ELISA, Technogenetics), fluoroenzymatic (FEIA, ThermoFisher) and chemiluminescence (CLIA, YHLO Biotech Co.) immunoassays.

Results

Diagnostic performance differed considerably between the assays, especially with regard to RF IgG isotype. Agreement among methods by Cohen’s kappa ranged from 0.05 (RF IgG CLIA vs. FEIA) to 0.846 (RF IgM CLIA vs. FEIA).

Conclusions

The poor agreement observed in this study indicates substantial lack of comparability among assays for RF isotypes. Harmonization of these tests requires further efforts before their measurement can be used in clinical practice.

Keywords: agreement; isotypes; nephelometry; rheumatoid arthritis; rheumatoid factor

Corresponding author: Maria Infantino, MD Laboratory of Immunology and Allergology, S. Giovanni di Dio Hospital, Via Torregalli, 3 50143, Florence, Italy, Phone: +390556932502, Fax: +390556932289, E-mail: maria2.infantino@uslcentro.toscana.it

Research funding: None declared.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Not applicable.
Ethical approval: Not applicable.

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Received: 2023-01-30

Accepted: 2023-03-17

Published Online: 2023-04-07

Published in Print: 2023-08-28

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Articles in the same Issue

https://doi.org/10.1515/cclm-2023-0109

Keywords for this article

agreement; isotypes; nephelometry; rheumatoid arthritis; rheumatoid factor