Laura Y.L. Kumar
Credit: LinkedIn
Methotrexate (MTX) treatment may lead to decreased antibody responses after vaccination in rheumatoid arthritis (RA) patients, and vaccine-induced CD4 T cell activation is reduced after treatment, according to a recent study. It turns out1.
“MTX is considered the gold standard for the treatment of RA and is also commonly used to treat other immune-mediated inflammatory diseases (IMIDs) such as psoriatic arthritis (PsA) and spondyloarthritis (SpA). It is mainly known for its effect of inhibiting the synthesis of purines and pyrimidines required for cell division, making it an important anti-cancer treatment, although the exact anti-inflammatory mechanism of MTX in IMID treatment is still unclear. Proposed mechanisms of action include increased adenosine release, inhibition of nuclear factor-κB (NF-κB) signaling, and increased expression of long intergenic non-coding RNAs that regulate inflammatory processes. , promoting the uncoupling of nitric oxide synthase leading to T cell apoptosis2,” said Laura YL Kummer, principal investigator and PhD student/research assistant. Sanquin Research’s Department of Immunopathology and colleagues wrote: 1
Kummer et al. reported data on 59 rheumatoid arthritis patients (including 18 RA patients receiving MTX monotherapy and 2 PsA patients), 10 RA patients not receiving immunosuppressive therapy, and 29 healthy controls. was analyzed. The researchers analyzed CD4 T and B cell responses seven days and three to six months after two SARS-CoV-2 messenger RNA vaccinations. They analyzed fresh whole blood using high-dimensional flow cytometry analysis, used an activation-induced marker assay to measure antigen-specific CD4 T cells, and used a spike probe to measure antigen-specific B cells. I studied cells. 1
Researchers found that seven days after two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. The frequency of spike-specific B cells was not affected.
Of note, the frequency of antigen-specific CD4 T cells was decreased in patients treated with MTX and strongly correlated with anti-RBD IgG antibodies, but not in healthy controls, indicating that CD4 It has been suggested that reduced T cell activity may slow vaccination antibody responses in MTX. patients who received treatment. Specifically, the median induction IQR for patients treated with MTX was 0.17 (95% CI, 0.12 to 0.21) compared with 0.29 (95% CI, 0.18 to 0.39) for patients not receiving MTX. ) (P = 0.017). The total number of CD4 T cells was not affected by MTX treatment. 1
“Overall, these data provide evidence of reduced vaccine-specific CD4 T cell responses in MTX-treated RA patients, which may be associated with reduced antibody kinetics in these patients. Although the extent to which reduced CD4 T cell responses impact clinical outcome in these patients remains unclear, CD4 T cell immunity in these patients may be reduced during future vaccinations or new infections. Furthermore, these data may contribute to elucidating the anti-inflammatory mechanism of action of MTX in immunomodulatory drugs,” concluded Kummer et al. Ta.
The researchers noted study limitations such as the relatively small number of participants, variable timing of sample collection, and a rare control population of rheumatoid arthritis patients not receiving systemic immunosuppressive therapy, which may have influenced disease activity in the study group. It was pointed out that this may have led to a bias toward lower prices. We were also unable to characterize spike-specific cTfh cells due to technical limitations.
References Kummer LYL, Fernández Blanco L, Kreher C On behalf of T2B! Immunology Research Group Against SARS-CoV-2 et al. Methotrexate treatment prevents induction of vaccine-specific CD4 T cell responses in patients with IMID. RMD Open 2024;10:e004664. doi: 10.1136/rmdopen-2024-004664Freeman ML, Clagett BM, Moisi D, et al. Methotrexate inhibits T cell proliferation, but not the expression of inflammatory cytokines that regulate immunity in people living with HIV. Front Immunol 2022;13:924718. doi:10.3389/fimmu.2022.92471
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