학술논문
Determination of the factors associated with antigen-specific CD4+ T-cell responses to BNT162b2 in patients with rheumatoid arthritis.
Document Type
Academic Journal
Author
Sagawa F; Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan.; Yamada H; Department of Clinical Immunology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan yamada.hisakata.579@m.kyushu-u.ac.jp.; Ayano M; Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan.; Kimoto Y; Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Japan.; Mitoma H; Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan.; Ono N; Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan.; Arinobu Y; Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan.; Kondo M; Kondo Clinic for Rheumatology and Orthopaedics, Fukuoka, Japan.; Nakashima Y; Department of Orthopedic Surgery, Kyushu University, Fukuoka, Japan.; Akashi K; Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan.; Horiuchi T; Fukuoka City Hospital, Fukuoka, Japan.; Niiro H; Department of Medical Education, Kyushu University, Fukuoka, Japan.
Source
Publisher: BMJ Publishing Group Country of Publication: England NLM ID: 101662038 Publication Model: Electronic Cited Medium: Internet ISSN: 2056-5933 (Electronic) Linking ISSN: 20565933 NLM ISO Abbreviation: RMD Open Subsets: MEDLINE
Subject
Language
English
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.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)