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Impaired cellular immune responses to herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors

Källmark, Hanna LU orcid ; Gullstrand, Birgitta LU ; Kahn, Fredrik LU ; Grenmyr, Elsa LU orcid ; Kahn, Robin LU ; Einarsson, Jon T. LU orcid ; Bengtsson, Anders A. LU and Kapetanovic, Meliha C. LU (2026) In Rheumatology 65(1).
Abstract

Objective: To investigate cellular immune responses to the herpes zoster (HZ) subunit (HZ/su) vaccine in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKis). Methods: RA patients treated with JAKi (n=46) at the Department of Rheumatology, Skåne University Hospital, Sweden, and healthy controls (n=37) received two doses of the HZ/su vaccine. Blood samples were collected before and ∼6weeks after vaccination. Varicella zoster virus (VZV) glycoprotein E (gE)-specific lymphocyte proliferation was analysed using flow cytometry. gE-specific production of tumour necrosis factor (TNF)α and IFNγ was analysed using an immunoassay. gE-specific responses were compared before and after vaccination within the groups... (More)

Objective: To investigate cellular immune responses to the herpes zoster (HZ) subunit (HZ/su) vaccine in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKis). Methods: RA patients treated with JAKi (n=46) at the Department of Rheumatology, Skåne University Hospital, Sweden, and healthy controls (n=37) received two doses of the HZ/su vaccine. Blood samples were collected before and ∼6weeks after vaccination. Varicella zoster virus (VZV) glycoprotein E (gE)-specific lymphocyte proliferation was analysed using flow cytometry. gE-specific production of tumour necrosis factor (TNF)α and IFNγ was analysed using an immunoassay. gE-specific responses were compared before and after vaccination within the groups (Wilcoxon signed-rank test), and between the patients and the controls (Mann–Whitney, ANCOVA). Proportions achieving a positive vaccine response were compared between the groups (Chi2 test). Results: Following vaccination, gE-specific proliferation of CD19+ cells increased significantly in both the patients (P=0.016) and the controls (P<0.001). For patients, no statistically significant differences were seen after vaccination for gE-specific proliferation of CD4+ or CD8+ cells or production of TNFα or IFNγ. Lower proportions of patients than the controls achieved a positive vaccine response for gE-specific proliferation of CD4+, CD8+ and CD19+ cells and gE-specific TNFα. Conclusion: The lack of significant increases in both vaccine-specific proliferation of CD4+ and CD8+ cells and proinflammatory cytokines after vaccination indicate impaired T cell responses to the HZ/su vaccination in patients with RA treated with JAKi. These results suggest that to ensure satisfactory cellular immunity in patients with RA, vaccination against HZ should preferably be performed before the initiation of JAKi treatment.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
herpes zoster, Janus kinase inhibitors, RA, vaccination, vaccine immunogenicity
in
Rheumatology
volume
65
issue
1
article number
keaf626
publisher
Oxford University Press
external identifiers
  • pmid:41330694
  • scopus:105029098835
ISSN
1462-0324
DOI
10.1093/rheumatology/keaf626
language
English
LU publication?
yes
id
2e04eb2a-5ce0-49dc-9c0e-8f0bc6f97ad1
date added to LUP
2026-02-20 15:20:16
date last changed
2026-02-20 15:21:14
@article{2e04eb2a-5ce0-49dc-9c0e-8f0bc6f97ad1,
  abstract     = {{<p>Objective: To investigate cellular immune responses to the herpes zoster (HZ) subunit (HZ/su) vaccine in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKis). Methods: RA patients treated with JAKi (n=46) at the Department of Rheumatology, Skåne University Hospital, Sweden, and healthy controls (n=37) received two doses of the HZ/su vaccine. Blood samples were collected before and ∼6weeks after vaccination. Varicella zoster virus (VZV) glycoprotein E (gE)-specific lymphocyte proliferation was analysed using flow cytometry. gE-specific production of tumour necrosis factor (TNF)α and IFNγ was analysed using an immunoassay. gE-specific responses were compared before and after vaccination within the groups (Wilcoxon signed-rank test), and between the patients and the controls (Mann–Whitney, ANCOVA). Proportions achieving a positive vaccine response were compared between the groups (Chi2 test). Results: Following vaccination, gE-specific proliferation of CD19+ cells increased significantly in both the patients (P=0.016) and the controls (P&lt;0.001). For patients, no statistically significant differences were seen after vaccination for gE-specific proliferation of CD4+ or CD8+ cells or production of TNFα or IFNγ. Lower proportions of patients than the controls achieved a positive vaccine response for gE-specific proliferation of CD4+, CD8+ and CD19+ cells and gE-specific TNFα. Conclusion: The lack of significant increases in both vaccine-specific proliferation of CD4+ and CD8+ cells and proinflammatory cytokines after vaccination indicate impaired T cell responses to the HZ/su vaccination in patients with RA treated with JAKi. These results suggest that to ensure satisfactory cellular immunity in patients with RA, vaccination against HZ should preferably be performed before the initiation of JAKi treatment.</p>}},
  author       = {{Källmark, Hanna and Gullstrand, Birgitta and Kahn, Fredrik and Grenmyr, Elsa and Kahn, Robin and Einarsson, Jon T. and Bengtsson, Anders A. and Kapetanovic, Meliha C.}},
  issn         = {{1462-0324}},
  keywords     = {{herpes zoster; Janus kinase inhibitors; RA; vaccination; vaccine immunogenicity}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Oxford University Press}},
  series       = {{Rheumatology}},
  title        = {{Impaired cellular immune responses to herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors}},
  url          = {{http://dx.doi.org/10.1093/rheumatology/keaf626}},
  doi          = {{10.1093/rheumatology/keaf626}},
  volume       = {{65}},
  year         = {{2026}},
}