Comparison of T cell response to vaccination in rheumatic patients treated with Janus kinase inhibitors and TNF inhibitors

Abstract Background Janus kinase inhibitors (JAKi) represent a well-established therapeutic option for the treatment of autoimmune diseases. However, there is a paucity of evidence regarding their impact on de novo immune responses to vaccinations. T cells may confer long-lasting immunity and cross-...

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Main Authors: Sebastian Hüper, Florian Eisele, Johannes Duell, Marc Schmalzing, Lea Nagler, Patrick Pascal Strunz, Matthias Froehlich, Jan Portegys, Michael Gernert
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Rheumatology
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Online Access:https://doi.org/10.1186/s41927-025-00542-7
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author Sebastian Hüper
Florian Eisele
Johannes Duell
Marc Schmalzing
Lea Nagler
Patrick Pascal Strunz
Matthias Froehlich
Jan Portegys
Michael Gernert
author_facet Sebastian Hüper
Florian Eisele
Johannes Duell
Marc Schmalzing
Lea Nagler
Patrick Pascal Strunz
Matthias Froehlich
Jan Portegys
Michael Gernert
author_sort Sebastian Hüper
collection DOAJ
description Abstract Background Janus kinase inhibitors (JAKi) represent a well-established therapeutic option for the treatment of autoimmune diseases. However, there is a paucity of evidence regarding their impact on de novo immune responses to vaccinations. T cells may confer long-lasting immunity and cross-recognise evolving epitopes of new viral variants, as evidenced by the SARS-CoV-2 vaccination. Consequently, we investigated the de novo T-cell response to SARS-CoV-2 vaccination in patients with rheumatic diseases undergoing treatment with JAK inhibitors. Methods Cross-sectional study, conducted in an outpatient department. Patients with rheumatic disease who had received two vaccinations against SARS-CoV-2 while under therapy with JAKi (n = 22) or tumour necrosis factor-blocking biologicals (TNFi) (control group n = 16) were recruited. To evaluate the vaccine-induced T cell response, the patients’ PBMCs were stimulated with SARS-CoV-2 spike protein peptides. The percentage of CD4+ T cells responding specifically to this stimulation by producing IFNγ was then measured using intracellular cytokine staining and flow cytometry. In addition antibody response to vaccination was assessed. Results A specific T cell response was detected in 11 out of 22 (50.0%) of patients in the JAKi cohort, compared to 13 out of 16 (81.3%) of the TNFi cohort (p = 0.088). Patients on JAKi had a lower percentage of CD4+ T cells responding to stimulation with SARS-CoV-2 spike peptides than patients on TNFi (p = 0.021). The proportion of patients with an antibody response and absolute anti-spike IgG levels did not significantly differ between the cohorts. Conclusions Patients on JAKi exhibited a compromised de novo T cell response to SARS-CoV-2 vaccination compared to TNFi patients. There is a need for further research on the effect of JAKi on T cell responses to vaccination.
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spelling doaj-art-92cf81a9129c476db5120c4c029979872025-08-20T04:02:44ZengBMCBMC Rheumatology2520-10262025-07-01911710.1186/s41927-025-00542-7Comparison of T cell response to vaccination in rheumatic patients treated with Janus kinase inhibitors and TNF inhibitorsSebastian Hüper0Florian Eisele1Johannes Duell2Marc Schmalzing3Lea Nagler4Patrick Pascal Strunz5Matthias Froehlich6Jan Portegys7Michael Gernert8Department of Internal Medicine II, Rheumatology/Clinical Immunology, University Hospital WürzburgDepartment of Internal Medicine II, Haematology and Oncology, University Hospital WürzburgDepartment of Internal Medicine II, Haematology and Oncology, University Hospital WürzburgDepartment of Internal Medicine II, Rheumatology/Clinical Immunology, University Hospital WürzburgDepartment of Internal Medicine II, Rheumatology/Clinical Immunology, University Hospital WürzburgDepartment of Internal Medicine II, Rheumatology/Clinical Immunology, University Hospital WürzburgDepartment of Internal Medicine II, Rheumatology/Clinical Immunology, University Hospital WürzburgDepartment of Internal Medicine II, Rheumatology/Clinical Immunology, University Hospital WürzburgDepartment of Internal Medicine II, Rheumatology/Clinical Immunology, University Hospital WürzburgAbstract Background Janus kinase inhibitors (JAKi) represent a well-established therapeutic option for the treatment of autoimmune diseases. However, there is a paucity of evidence regarding their impact on de novo immune responses to vaccinations. T cells may confer long-lasting immunity and cross-recognise evolving epitopes of new viral variants, as evidenced by the SARS-CoV-2 vaccination. Consequently, we investigated the de novo T-cell response to SARS-CoV-2 vaccination in patients with rheumatic diseases undergoing treatment with JAK inhibitors. Methods Cross-sectional study, conducted in an outpatient department. Patients with rheumatic disease who had received two vaccinations against SARS-CoV-2 while under therapy with JAKi (n = 22) or tumour necrosis factor-blocking biologicals (TNFi) (control group n = 16) were recruited. To evaluate the vaccine-induced T cell response, the patients’ PBMCs were stimulated with SARS-CoV-2 spike protein peptides. The percentage of CD4+ T cells responding specifically to this stimulation by producing IFNγ was then measured using intracellular cytokine staining and flow cytometry. In addition antibody response to vaccination was assessed. Results A specific T cell response was detected in 11 out of 22 (50.0%) of patients in the JAKi cohort, compared to 13 out of 16 (81.3%) of the TNFi cohort (p = 0.088). Patients on JAKi had a lower percentage of CD4+ T cells responding to stimulation with SARS-CoV-2 spike peptides than patients on TNFi (p = 0.021). The proportion of patients with an antibody response and absolute anti-spike IgG levels did not significantly differ between the cohorts. Conclusions Patients on JAKi exhibited a compromised de novo T cell response to SARS-CoV-2 vaccination compared to TNFi patients. There is a need for further research on the effect of JAKi on T cell responses to vaccination.https://doi.org/10.1186/s41927-025-00542-7Janus kinase inhibitorsVaccinationT cell responseSARS-CoV-2 vaccinationJAK- inhibitorsTH1-response
spellingShingle Sebastian Hüper
Florian Eisele
Johannes Duell
Marc Schmalzing
Lea Nagler
Patrick Pascal Strunz
Matthias Froehlich
Jan Portegys
Michael Gernert
Comparison of T cell response to vaccination in rheumatic patients treated with Janus kinase inhibitors and TNF inhibitors
BMC Rheumatology
Janus kinase inhibitors
Vaccination
T cell response
SARS-CoV-2 vaccination
JAK- inhibitors
TH1-response
title Comparison of T cell response to vaccination in rheumatic patients treated with Janus kinase inhibitors and TNF inhibitors
title_full Comparison of T cell response to vaccination in rheumatic patients treated with Janus kinase inhibitors and TNF inhibitors
title_fullStr Comparison of T cell response to vaccination in rheumatic patients treated with Janus kinase inhibitors and TNF inhibitors
title_full_unstemmed Comparison of T cell response to vaccination in rheumatic patients treated with Janus kinase inhibitors and TNF inhibitors
title_short Comparison of T cell response to vaccination in rheumatic patients treated with Janus kinase inhibitors and TNF inhibitors
title_sort comparison of t cell response to vaccination in rheumatic patients treated with janus kinase inhibitors and tnf inhibitors
topic Janus kinase inhibitors
Vaccination
T cell response
SARS-CoV-2 vaccination
JAK- inhibitors
TH1-response
url https://doi.org/10.1186/s41927-025-00542-7
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