RMD Open (Oct 2024)

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

  • ,
  • Sander W Tas,
  • Joep Killestein,
  • Joost Raaphorst,
  • Taco W Kuijpers,
  • Alexandre E Voskuyl,
  • Gertjan Wolbink,
  • Theo Rispens,
  • Anneke J van der Kooi,
  • Anja Ten Brinke,
  • Karina de Leeuw,
  • Abraham Rutgers,
  • Juan J Garcia-Vallejo,
  • Frederike J Bemelman,
  • YK Onno Teng,
  • Phyllis I Spuls,
  • Mark Löwenberg,
  • Jelle de Wit,
  • Diane van der Woude,
  • Marcel W Bekkenk,
  • Luuk Wieske,
  • Esther Brusse,
  • Laura Boekel,
  • Filip Eftimov,
  • Eileen W Stalman,
  • Maurice Steenhuis,
  • Sofie Keijzer,
  • Olvi Cristianawati,
  • Koos P J van Dam,
  • Adriaan G Volkers,
  • Annelie H Musters,
  • Nicoline F Post,
  • Angela L Bosma,
  • Marc L Hilhorst,
  • Yosta Vegting,
  • Bo Broens,
  • Barbara Horváth,
  • Annabel M Ruiter,
  • Matthias H Busch,
  • Dirk Jan Hijnen,
  • Niels J M Verstegen,
  • Pieter A van Doorn,
  • Jan JGM Verschuuren,
  • Laura Y L Kummer,
  • Ruth R Hagen,
  • Christine Kreher,
  • Lisan H Kuijper,
  • Mariël C Duurland,
  • Veronique A L Konijn,
  • Carolien E van de Sandt,
  • Laura Fernández Blanco,
  • Amélie Bos,
  • Charlotte Menage,
  • Tineke Jorritsma,
  • Jet van den Dijssel,
  • Rivka de Jongh,
  • Tom Ashhurst,
  • Marit J van Gils,
  • Mathieu Claireaux,
  • Sija Marieke van Ham,
  • Renée CF van Allaart,
  • Adája E Baars,
  • George Elias,
  • Cécile ACM van Els,
  • Marit J van Gils,
  • H Stephan Goedee,
  • Geert RAM D’Haens,
  • Papay BP Jallah,
  • Elham S Mirfazeli,
  • Jim BD Keijser,
  • Lotte van Ouwerkerk,
  • Pieter van Paassen,
  • Agner R Parra Sanchez,
  • W Ludo van der Pol,
  • Corine RG Schreurs,
  • R Bart Takkenberg,
  • Koos AH Zwinderman

DOI
https://doi.org/10.1136/rmdopen-2024-004664
Journal volume & issue
Vol. 10, no. 4

Abstract

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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.Trial registration number NL8900.