Immunosuppressants in dermatology on vaccine immunogenicity: a prospective cohort study of pemphigus patients in the pandemic

Front Immunol. 2024 Nov 22:15:1506962. doi: 10.3389/fimmu.2024.1506962. eCollection 2024.

Abstract

Introduction: Both cellular and humoral responses are important for vaccine protection, but recommendations on immunosuppressants in dermatology are largely based on pre-pandemic experiences. This study aimed to investigate the impacts of immunosuppressants on humoral and cellular immunogenicity to COVID-19 vaccinations in pemphigus patients.

Methods: SARS-CoV-2-naïve pemphigus patients and age-, and sex-matched healthy controls were recruited from multiple tertiary medical centers during 2021-2023. Anti-spike protein-related T-cell responses, antibody titers, and high-parameter cell analysis of the peripheral blood were utilized to investigate the inhibitory effects of immunosuppressants, including rituximab and azathioprine.

Results: A total of 32 patients and 120 healthy controls were enrolled. COVID-19 vaccinations spaced at least six months after the last rituximab infusion did not cause a significant difference in anti-viral T-cell or antibody responses between rituximab-naïve and rituximab-treated patients. All pemphigus patients demonstrated improved antibody responses after the third vaccination and none of them suffered from severe COVID-19 illness. Intriguingly, we found that daily dosages of 100 mg or more of azathioprine were linked to significantly decreased anti-viral T-cell responses induced by the vaccination (mean of fold change [SD]; higher azathioprine dosage = 0.70 [0.61] folds vs. lower azathioprine dosage = 2.11 [1.03] folds; p = 0.044).

Conclusion: Except for a subset of patients with unrecovered B-cell deficiency, rituximab infusion with proper scheduling of vaccination preserved better anti-viral T-cell responses and did not lead to hindered antibody responses in pemphigus patients. All pemphigus patients benefited from receiving the third booster regardless of B-cell status.

Keywords: anti-viral humoral immunity; anti-viral t-cell response; azathioprine; pemphigus vulgaris; rituximab; vaccine immunogenicity.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Azathioprine* / therapeutic use
  • COVID-19 Vaccines* / immunology
  • COVID-19 Vaccines* / therapeutic use
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Female
  • Humans
  • Immunogenicity, Vaccine*
  • Immunosuppressive Agents* / therapeutic use
  • Male
  • Middle Aged
  • Pemphigus* / drug therapy
  • Pemphigus* / immunology
  • Prospective Studies
  • Rituximab* / therapeutic use
  • SARS-CoV-2* / immunology
  • T-Lymphocytes / immunology

Substances

  • Immunosuppressive Agents
  • Rituximab
  • COVID-19 Vaccines
  • Azathioprine
  • Antibodies, Viral

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-182A-113 -MY3 and 110-2320-B-182A-014 -MY3), and Chang Gung Memorial Hospital (CMRPG3M1521-3). The study sponsors had no role in the design and conduct of the study; collection, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.