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

Area of Science:

• Immunology
• Rheumatology
• Vaccinology

Background:

• Methotrexate (MTX) is a common treatment for rheumatoid arthritis (RA), but its effects on cellular immunity and vaccine responses are not fully understood.
• This knowledge gap raises concerns about infection risk and vaccine efficacy in MTX-treated patients.

Purpose of the Study:

• To investigate the impact of MTX on B and CD4 T cell responses following SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases.
• To compare immune responses between MTX-treated patients, untreated RA patients, and healthy controls.

Main Methods:

• Studied 18 RA patients and 2 psoriatic arthritis patients on MTX monotherapy, 10 RA patients without immunosuppressants, and 29 healthy controls.
• Analyzed CD4 T and B cell responses 7 days and 3-6 months post-two-dose SARS-CoV-2 mRNA vaccination.
• Utilized high-dimensional flow cytometry, activation-induced marker assays for CD4 T cells, and spike probes for B cells.

Main Results:

• No significant differences in total B and T cell counts or spike-specific B cell frequencies were observed between MTX-treated patients and controls 7 days post-vaccination.
• A notable reduction in antigen-specific CD4 T cells was found in MTX-treated patients, correlating with anti-RBD IgG antibody levels.
• These findings suggest MTX may impair CD4 T cell activity, potentially delaying antibody responses after vaccination.

Conclusions:

• MTX treatment demonstrably reduces vaccine-induced CD4 T cell activation.
• This reduction in CD4 T cell activity correlates with diminished antibody responses following SARS-CoV-2 vaccination.
• Further research is needed to fully elucidate the clinical implications for infection and vaccination in MTX-treated populations.