Biomedicines (Mar 2023)

Evaluation of Specific Cellular and Humoral Immune Response to <i>Toxoplasma gondii</i> in Patients with Autoimmune Rheumatic Diseases Immunomodulated Due to the Use of TNF Blockers

  • Cristhianne Molinero Ratkevicius Andrade,
  • Aline Caroline de Lima Marques,
  • Rodolfo Pessato Timóteo,
  • Ana Carolina de Morais Oliveira-Scussel,
  • Fernanda Bernadelli De Vito,
  • Marcos Vinícius da Silva,
  • José Roberto Mineo,
  • Reginaldo Botelho Teodoro,
  • Denise Bertulucci Rocha Rodrigues,
  • Virmondes Rodrigues Júnior

DOI
https://doi.org/10.3390/biomedicines11030930
Journal volume & issue
Vol. 11, no. 3
p. 930

Abstract

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(1) Background: TNF antagonists have been used to treat autoimmune diseases (AD). However, during the chronic phase of toxoplasmosis, TNF-α and TNFR play a significant role in maintaining disease resistance and latency. Several studies have demonstrated the risk of latent infections’ reactivation in patients infected with toxoplasmosis. Our objective was to verify whether patients with autoimmune rheumatic diseases, who use TNF antagonists and/or synthetic drugs and had previous contact with Toxoplasma gondii (IgG+), present any indication of an increased risk of toxoplasmosis reactivation. (2) Methods: Blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were evaluated after stimulation with antigens of Toxoplasma gondii, with anti-CD3/anti-CD28 or without stimulus, at 48 and 96 h. CD69+, CD28+, and PD-1 stains were evaluated, in addition to intracellular expression of IFN-γ, IL-17, and IL-10 by CD4+ and the presence of regulatory CD4+ T cells by labeling CD25+, FOXP3, and LAP. The cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 were measured in the culture supernatant after 96 h. Serology for IgG and IgG1 was evaluated. (3) Results: There were no differences in the levels of IgG and IgG1 between the groups, but the IgG1 avidity was reduced in the immunobiological group compared to the control group. All groups exhibited a significant correlation between IgG and IgG1 positivity. CD4+ T lymphocytes expressing PD-1 were increased in individuals suffering from autoimmune rheumatic diseases and using disease-modifying antirheumatic drugs. In addition, treatment with TNF blockers did not seem to influence the populations of regulatory T cells and did not interfere with the expression of the cytokines IFN-γ, IL-17, and IL-10 by CD4+ cells or the production of cytokines by PBMCs from patients with AD. (4) Conclusions: This study presents evidence that the use of TNF-α blockers did not promote an immunological imbalance to the extent of impairing the anti-Toxoplasma gondii immune response and predisposing to toxoplasmosis reactivation.

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