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Licensed Unlicensed Requires Authentication Published by De Gruyter July 6, 2022

IgA rheumatoid factor in rheumatoid arthritis

  • Lieve Van Hoovels ORCID logo EMAIL logo , Bert Vander Cruyssen , Daniela Sieghart , Carolien Bonroy , Eszter Nagy , Rille Pullerits , Saša Čučnik , Charlotte Dahle , Ingmar Heijnen , Luca Bernasconi ORCID logo , Farid Benkhadra , Laura Bogaert , Stefanie Van Den Bremt , Ann Van Liedekerke , Geert Vanheule , Johan Robbrecht , Lucy Studholme , Claudine Wirth , Rüdiger Müller , Diego Kyburz , Christopher Sjöwall ORCID logo , Alf Kastbom , Rok Ješe , Boja Jovancevic , Emese Kiss , Peggy Jacques , Daniel Aletaha , Guenter Steiner , Patrick Verschueren and Xavier Bossuyt ORCID logo EMAIL logo



Rheumatoid factor (RF) is a well-established marker for the diagnosis and classification of rheumatoid arthritis (RA). Most studies evaluated IgM RF or isotype-nonspecific total RF assays. We evaluated the added value of IgA RF in this context.


An international sample cohort consisting of samples from 398 RA patients and 1073 controls was tested for IgA RF with 3 commercial assays. For all RA patients and 100 controls essential clinical and serological data for ACR/EULAR classification were available.


The sensitivity of IgA RF for diagnosing RA was lower than the sensitivity of IgM RF. Differences in numerical values between IgA RF assays were observed. With all assays, the highest IgA RF values were found in patients with primary Sjögren’s syndrome. Double positivity for IgM RF and IgA RF had a higher specificity for RA than either IgM RF or IgA RF. The sensitivity of double positivity was lower than the sensitivity of either IgA RF or IgM RF. Single positivity for IgA RF was at least as prevalent in controls than in RA patients. Adding IgA RF to IgM RF and anti-citrullinated protein antibodies (ACPA) did not affect RA classification. However, combined positivity for IgA RF, IgM RF and IgG ACPA had a higher specificity and lower sensitivity for RA classification than positivity for either of the antibodies.


IgA RF showed a lower sensitivity than IgM RF. Combining IgA RF with IgM RF and ACPA did not improve sensitivity of RA classification. Combined positivity (IgA-RF/IgM-RF/ACPA) increased specificity.

Corresponding authors: Xavier Bossuyt, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; and Department of Laboratory Medicine, University Hospital Leuven, Herestraat 49, 3000 Leuven, Belgium, Phone: 0032-16-347902, Fax: 0032-16-347010, E-mail: ; and Lieve Van Hoovels, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; and Department of Laboratory Medicine, OLV Hospital, Moorselbaan 164, 9300 Aalst, Belgium, Phone: 0032-53724791, Fax: 0032-53-724588, E-mail:

Funding source: Phadia AB

Award Identifier / Grant number: In-kind provision of RF/ACPA reagents

Funding source: Thermo Fisher Scientific

Award Identifier / Grant number: In-kind provision of RF/ACPA reagents

Funding source: Orgentec

Award Identifier / Grant number: In-kind provision of RF/ACPA reagents

Funding source: Cambridge Life Science

Award Identifier / Grant number: In-kind provision of RF/ACPA reagents


We thank all participating diagnostic companies for in-kind provision of the assays, technical training and support and the constructive discussions. Furthermore, we are very thankful to the laboratory technicians of all participating laboratories for their most appreciated assistance in the performance of the RF/ACPA analyses.

  1. Research funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. All participating diagnostic companies in-kind provided the RF/ACPA assays, technical training and support free of charge (see competing interests).

  2. Author contributions: LVH, XB, BVDC, DS, GS, PV contributed to the study conception and design. Patient samples were selected by LVH, BVDC, DS, DA, PV, CB, EN, RP, SC, CD, IH, LB, FB, CW, RM, DK, CS, AK, RJ, BJ, EK and PJ. Material preparation and data collection was performed by LS, SVDB, LB, LVH, AV, GV, JR; data analysis by LVH and XB. Manuscript was prepared by LVH, XB, DS and GS and commented by all authors. The final manuscript was read and approved by all authors. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: XB, LVH, GS and DS have received speaker fees from Thermo Fisher Scientific and have been a consultant for Thermo Fisher Scientific; LB and IH have received speaker fees from Thermo Fisher Scientific. All participating diagnostic companies in-kind supported with RF/ACPA assays and technical training: Thermo Fisher Scientific, Phadia AB, Uppsala, Sweden; Cambridge Life Science, Ely, UK; Orgentec, Mainz, Germany.

  4. Informed consent: Informed consent was obtained if applicable for individuals included in this study.

  5. Ethical approval: Ethical approval was granted by the Institutional Review Board of University Hospital Leuven and OLV Hospital Aalst with Belgian registration number: B322201939877.

  6. Data availability: All data relevant to the study are included in the article or uploaded as supplementary information.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2022-03-15
Accepted: 2022-06-22
Published Online: 2022-07-06
Published in Print: 2022-09-27

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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