Determination of the Factors Associated with Antigen-specific CD4+ T-cell Responses to BNT162b2 in Patients with Rheumatoid Arthritis

Overview

Journal RMD Open

Publisher BMJ Publishing Group

Specialty Rheumatology

Date 2024 Jan 12

PMID 38216287

Authors

Fumiaki Sagawa

Hisakata Yamada

Masahiro Ayano

Yasutaka Kimoto

Hiroki Mitoma

Nobuyuki Ono

Yojiro Arinobu

Masakazu Kondo

Yasuharu Nakashima

Koichi Akashi

Takahiko Horiuchi

Hiroaki Niiro

Affiliations

Soon will be listed here.

Abstract

Objectives: Understanding interpatient variation in CD4+T-cell responses is the bases for understanding the pathogenesis and management of rheumatoid arthritis (RA). We examined immune responses to SARS-CoV-2 vaccine in a cohort of patients with RA and determined factors associated with the responses.

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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