Methotrexate reduces circulating Th17 cells and impairs plasmablast and memory B cell expansions following...

Area of Science:

• Immunology
• Rheumatology
• Vaccinology

Background:

• Rheumatoid arthritis (RA) patients often receive disease-modifying drugs, including methotrexate (MTX).
• MTX is known to potentially impair vaccine responses.
• Understanding the cellular mechanisms behind impaired vaccine response in RA patients on MTX is crucial for optimizing immunization strategies.

Purpose of the Study:

• To investigate the impact of MTX on B and T cell phenotypes following pneumococcal conjugate vaccine (PCV) administration in RA patients.
• To compare immune cell responses in RA patients on MTX, RA patients without MTX, and healthy controls (HC).

Main Methods:

• Flow cytometry was used to analyze B and T cell subsets in peripheral blood.
• Multiplex bead assay quantified serotype-specific IgG antibody levels pre- and post-vaccination.
• Study included RA patients on MTX (MTX group), RA patients without disease-modifying drugs (0DMARD), and healthy controls (HC).

Main Results:

• PCV vaccination increased plasmablasts and switched memory B cells in HC and 0DMARD groups, but not in the MTX group.
• Post-immunization plasmablast levels were significantly lower in the MTX group compared to 0DMARD and HC groups.
• MTX treatment led to a decrease in Th17 cells, while HC showed an increase post-immunization.
• Post-immunization plasmablasts correlated with the mean antibody response ratio in all RA patients.

Conclusions:

• Methotrexate significantly impairs the activation of plasmablasts and switched memory B cells following PCV challenge in RA patients.
• MTX reduces Th17 cell populations, potentially affecting adaptive immunity.
• These findings highlight the need for careful consideration of vaccination timing and strategies in RA patients undergoing MTX therapy.