Determination of the factors associated with antigen-specific CD4+ T-cell responses to BNT162b2 in patients with rheumatoid arthritis

确定类风湿关节炎患者对 BNT162b2 的抗原特异性 CD4+ T 细胞反应相关因素

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作者:Fumiaki Sagawa, Hisakata Yamada, Masahiro Ayano, Yasutaka Kimoto, Hiroki Mitoma, Nobuyuki Ono, Yojiro Arinobu, Masakazu Kondo, Yasuharu Nakashima, Koichi Akashi, Takahiko Horiuchi, Hiroaki Niiro

Conclusions

Clinical and immunological variables that are associated with antigen-specific CD4 T-cell responses in patients with RA were determined by analysing immune responses against SARS-CoV-2 vaccine.

Methods

Four hundred and thirty-one patients with RA having received two doses of BNT162b2, a messenger RNA-based vaccine for SARS-CoV-2, were included. Vaccine antigen-specific IgG was detected by ELISA, and antigen-specific CD4+T cells were detected by CD154 expression in response to antigenic stimulation. Expression of cytokines was concomitantly detected by intracellular staining. Associations among background variables, antigen-specific antibody production and the CD4+T-cell responses were analysed. Unsupervised hierarchical clustering was performed based on the profiles of antigen-specific cytokine production by CD4+T cells to stratify patients with RA.

Results

Multivariate analysis indicated that ageing negatively affects CD4+T-cell response as well as antibody production. No association was detected between the presence or the levels of rheumatoid factor/anti-cyclic citrullinated peptide antibody and anti-vaccine immune responses. Methotrexate and prednisolone reduced B cell but not T-cell responses. Conventional immunophenotyping by the expression of chemokine receptors was not associated with the actual CD4+T-cell response, except for T helper cells (Th1). Functional immunophenotyping based on the profiles of antigen-specific cytokine production of CD4+T cells stratified patients with RA into three clusters, among which Th1-dominant type less frequently underwent joint surgery. Conclusions: Clinical and immunological variables that are associated with antigen-specific CD4 T-cell responses in patients with RA were determined by analysing immune responses against SARS-CoV-2 vaccine.

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