W101 - Methotrexate Reduces Post-vaccination Antigen-specific T Cell Response in Children with Juvenile Idiopathic Arthritis

Abstract Text: Juvenile Idiopathic Arthritis (JIA) is a chronic, T-cell-driven auto-immune disease that causes destructive, erosive joint inflammation. Its treatment involves immunosuppression with disease-modifying anti-rheumatic drugs (DMARDs), which can potentially vaccine-induced immune responses and compromise protection against infection. Hence, there is a critical unmet medical need to delineate the DMARD effects on vaccine response to rationalise the vaccination strategy in these vulnerable patients.
To address this unmet need, we interrogated the effects of methotrexate (MTX) on the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) specific T-cell immune response in JIA patients (N=79) before and after receiving their first and second vaccine doses. Peripheral blood mononuclear cells (PBMCs) were stimulated with SARS-CoV-2 peptide pools for mass cytometry. Increased expression of activation-induced markers (AIM+), CD154 and CD69, defined antigen-specific CD4+ T-cells. Median with interquartile ranges and Mann-Whitney U test were performed.
Importantly, we found that with MTX treatment, the frequency of CD4+ AIM+ SARS-CoV-2 Spike-specific T-cells was significantly reduced only after the second vaccination 0.60 (0.412-0.89)% versus 0.41 (0.26-0.79)% for no MTX versus MTX respectively (p=0.015). Moreover, for those on long-term MTX treatment, withholding MTX one week before the first and second vaccine doses significantly increased CD4+ AIM+ SARS-CoV-2 Spike-specific T-cells: 0.27 (0.20-0.36)% versus 0.49 (0.35-1.20)% for MTX versus MTX withheld respectively (p=0.0063).
MTX negatively impacts the strength of the antigen-specific CD4+ T-cell response after COVID-19 mRNA vaccination, withholding MTX can ameliorate this and increase the CD4+ AIM+ antigen-specific T cells. Translationally, this knowledge will help to refine the vaccine strategy in an evidence-based manner.