Methotrexate treatment hampers induction of vaccine-specific CD4 T cell responses in patients with IMID

  • T2B! immunity against SARS-CoV-2 study group
  • , Laura Y.L. Kummer
  • , Laura Fernández Blanco
  • , Christine Kreher
  • , Amélie Bos
  • , Lisan H. Kuijper
  • , Niels J.M. Verstegen
  • , Carolien E. Van De Sandt
  • , Veronique A.L. Konijn
  • , Mariël C. Duurland
  • , Charlotte Menage
  • , Tineke Jorritsma
  • , Maurice Steenhuis
  • , Ruth R. Hagen
  • , Jet Van Den Dijssel
  • , Rivka De Jongh
  • , Tom Ashhurst
  • , Marit J. van Gils
  • , Juan J. Garcia-Vallejo
  • , Mathieu Claireaux
  • Eileen W. Stalman, Koos P.J. Van Dam, Luuk Wieske, Laura Boekel, Gertjan Wolbink, Sander W. Tas, Theo Rispens, Taco W. Kuijpers, Filip Eftimov, Sija Marieke Van Ham, Anja Ten Brinke*
*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
7 Downloads (Pure)

Abstract

Objectives: Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.

Methods: In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3-6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.

Results: Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.

Conclusion: Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.

Original languageEnglish
Article numbere004664
Number of pages12
JournalRMD Open
Volume10
Issue number4
DOIs
Publication statusPublished - 7-Oct-2024

Keywords

  • autoimmune diseases
  • B-lymphocytes
  • methotrexate
  • T-lymphocytes

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