The impact of the mRNA COVID-19 vaccine on the Th-like cytokine profile in individuals with no history of COVID-19: insights into autoimmunity targeting heat shock proteins

Front Immunol. 2025 Mar 14:16:1549739. doi: 10.3389/fimmu.2025.1549739. eCollection 2025.

Abstract

Although some reports suggest that COVID-19 vaccination may exacerbate existing autoimmune diseases or trigger new-onset cases, a definitive causal relationship between the vaccines and these conditions has not been established. Several potential mechanisms have been proposed to explain this association, including: (i) molecular mimicry, which refers to a structural similarity between SARS-CoV-2 and human antigens; (ii) bystander activation, involving both B and T lymphocytes; and (iii) the effects of adjuvants. In this study, we investigated whether two doses of the mRNA COVID-19 vaccine influenced blood cytokine levels associated with major T helper cell populations, which are known to play a significant role in autoimmunity and revisited the role of the humoral autoimmune response directed against heat shock proteins (Hsps) in individuals with no history of COVID-19. While no significant differences were found in the levels of IFN-γ, IL-6, IL-22, IL-4, IL-8, IL-10, and IL-17A, between vaccinated and unvaccinated people, several positive correlations were observed between serum cytokine levels and circulating autoantibodies directed against self-Hsps exclusively in vaccinated individuals. These findings suggest that the mRNA COVID-19 vaccine does not impact cytokines involved in the pathogenesis of autoimmune diseases. Further research is required to evaluate the safety of COVID-19 vaccination in patients with autoimmune conditions, particularly those in whom anti-Hsps autoantibodies are suspected to contribute to disease development.

Keywords: COVID-19; SARS-CoV-2; T helper cells; cytokines; heat shock proteins; vaccine.

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Autoimmunity* / immunology
  • COVID-19 Vaccines* / adverse effects
  • COVID-19 Vaccines* / immunology
  • COVID-19* / immunology
  • COVID-19* / prevention & control
  • Cytokines* / blood
  • Cytokines* / immunology
  • Female
  • Heat-Shock Proteins* / immunology
  • Humans
  • Male
  • Middle Aged
  • SARS-CoV-2* / immunology
  • T-Lymphocytes, Helper-Inducer* / immunology
  • Vaccination

Substances

  • Cytokines
  • Heat-Shock Proteins
  • COVID-19 Vaccines
  • Autoantibodies