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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1568439
Beyond interferon gamma -decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases
Provisionally accepted
Jakub Wroński *
Magdalena Massalska 
Bożena Jaszczyk 
Anna Felis-Giemza Anna Kornatka Magdalena Plebańczyk Tomasz Burakowski Brygida Kwiatkowska 
Ewa Kuca-Warnawin 
Marzena Ciechomska - National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
The global COVID-19 pandemic has led to significant advancements in vaccine research, particularly regarding patients with autoimmune inflammatory rheumatic diseases (AIIRD). However, most studies have assessed the post-vaccination cellular response only by measuring the production of interferon-gamma. This study aimed to explore the post-vaccination cellular immune response in patients with AIIRD, with a focus on the effects of immunomodulatory drugs on different proteins involved in the cellular response and cytotoxicity. We analyzed blood samples from 54 patients -16 healthy controls (HC) and 38 AIIRD patients -at three time points: before (T0), 4 weeks after (T1), and more than 6 months after (T2) a COVID-19 booster vaccination. Gene expression and concentration levels of 13 proteins involved in cellular immunity were assessed. Our study showed significantly reduced production of TNF at T0, IL-2 at T0 and T2, and perforin at T2 in AIIRD patients compared to HC. In AIIRD patients the expression of genes involved in cytotoxicity, including NRF2, TRAIL, cathepsin B, and cathepsin H was impaired. Both protein concentrations and gene expression were particularly altered in those treated with glucocorticoids, methotrexate, and biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Among b/tsDMARDs only IL-17 inhibitors did not affect the cellular response. These findings suggest that COVID-19 vaccination elicits a weakened cellular response in patients with AIIRD, particularly those on immunosuppressive therapies, potentially compromising vaccine efficacy. Further studies are required to determine the clinical impact of these findings on long-term vaccine effectiveness in this population.
Keywords: COVID-19, Autoimmune inflammatory rheumatic diseases, Cellular Immune Response, Vaccination, Immunomodulatory drugs
Received: 03 Feb 2025; Accepted: 10 Mar 2025.
Copyright: © 2025 Wroński, Massalska, Jaszczyk, Felis-Giemza, Kornatka, Plebańczyk, Burakowski, Kwiatkowska, Kuca-Warnawin and Ciechomska. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jakub Wroński, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
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