AUTHOR=Keijzer Sofie , Oskam Nienke , Ooijevaar-de Heer Pleuni , Steenhuis Maurice , Keijser Jim B.D. , Wieske Luuk , van Dam Koos P.J. , Stalman Eileen W. , Kummer Laura Y.L. , Boekel Laura , Kuijpers Taco W. , ten Brinke Anja , van Ham S. Marieke , Eftimov Filip , Tas Sander W. , Wolbink Gerrit J. , Rispens Theo TITLE=Longitudinal rheumatoid factor autoantibody responses after SARS-CoV-2 vaccination or infection JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1314507 DOI=10.3389/fimmu.2024.1314507 ISSN=1664-3224 ABSTRACT=Background

Rheumatoid factors (RFs) are autoantibodies that target the Fc region of IgG, and are found in patients with rheumatic diseases as well as in the healthy population. Many studies suggest that an immune trigger may (transiently) elicit RF responses. However, discrepancies between different studies make it difficult to determine if and to which degree RF reactivity can be triggered by vaccination or infection.

Objective

We quantitatively explored longitudinal RF responses after SARS-CoV-2 vaccination and infection in a well-defined, large cohort using a dual ELISA method that differentiates between true RF reactivity and background IgM reactivity. In addition, we reviewed existing literature on RF responses after vaccination and infection.

Methods

151 healthy participants and 30 RA patients were included to measure IgM-RF reactivity before and after SARS-CoV-2 vaccinations by ELISA. Additionally, IgM-RF responses after a SARS-CoV-2 breakthrough infection were studied in 51 healthy participants.

Results

Published prevalence studies in subjects after infection report up to 85% IgM-RF seropositivity. However, seroconversion studies (both infection and vaccination) report much lower incidences of 2-33%, with a trend of lower percentages observed in larger studies. In the current study, SARS-CoV-2 vaccination triggered low-level IgM-RF responses in 5.5% (8/151) of cases, of which 1.5% (2/151) with a level above 10 AU/mL. Breakthrough infection was accompanied by development of an IgM-RF response in 2% (1/51) of cases.

Conclusion

Our study indicates that de novo RF induction following vaccination or infection is an uncommon event, which does not lead to RF epitope spreading.