Beyond interferon gamma - decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases

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-gam...

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Main Authors: Jakub Wroński, Magdalena Massalska, Bożena Jaszczyk, Anna Felis-Giemza, Anna Kornatka, Magdalena Plebańczyk, Tomasz Burakowski, Brygida Kwiatkowska, Ewa Kuca-Warnawin, Marzena Ciechomska
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568439/full
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author Jakub Wroński
Magdalena Massalska
Bożena Jaszczyk
Anna Felis-Giemza
Anna Kornatka
Magdalena Plebańczyk
Tomasz Burakowski
Brygida Kwiatkowska
Ewa Kuca-Warnawin
Marzena Ciechomska
author_facet Jakub Wroński
Magdalena Massalska
Bożena Jaszczyk
Anna Felis-Giemza
Anna Kornatka
Magdalena Plebańczyk
Tomasz Burakowski
Brygida Kwiatkowska
Ewa Kuca-Warnawin
Marzena Ciechomska
author_sort Jakub Wroński
collection DOAJ
description 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.
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spelling doaj-art-4438d8e93a4d400a98d1a5030c7571ad2025-08-20T03:42:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15684391568439Beyond interferon gamma - decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseasesJakub Wroński0Magdalena Massalska1Bożena Jaszczyk2Anna Felis-Giemza3Anna Kornatka4Magdalena Plebańczyk5Tomasz Burakowski6Brygida Kwiatkowska7Ewa Kuca-Warnawin8Marzena Ciechomska9Department of Rheumatology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Outpatient Clinics, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandBiologic Therapy Center, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Early Arthritis, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandDepartment of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, PolandThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568439/fullCOVID-19autoimmune inflammatory rheumatic diseasescellular immune responsevaccinationimmunomodulatory drugs
spellingShingle Jakub Wroński
Magdalena Massalska
Bożena Jaszczyk
Anna Felis-Giemza
Anna Kornatka
Magdalena Plebańczyk
Tomasz Burakowski
Brygida Kwiatkowska
Ewa Kuca-Warnawin
Marzena Ciechomska
Beyond interferon gamma - decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases
Frontiers in Immunology
COVID-19
autoimmune inflammatory rheumatic diseases
cellular immune response
vaccination
immunomodulatory drugs
title Beyond interferon gamma - decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases
title_full Beyond interferon gamma - decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases
title_fullStr Beyond interferon gamma - decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases
title_full_unstemmed Beyond interferon gamma - decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases
title_short Beyond interferon gamma - decreased cellular response to COVID-19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases
title_sort beyond interferon gamma decreased cellular response to covid 19 vaccination booster in patients with autoimmune inflammatory rheumatic diseases
topic COVID-19
autoimmune inflammatory rheumatic diseases
cellular immune response
vaccination
immunomodulatory drugs
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1568439/full
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