Avaliação da resposta imune celular e humoral específica ao Toxoplasma godii em pacientes imunomodulados devido ao uso de bloqueadores de TNF

Abstract

Toxoplasmosis is one of the most prevalent zoonoses in Brazil and in the world and can have serious consequences in immunosuppressed patients. For this reason, there is great concern with the prevention and monitoring of acute toxoplasmosis in these groups of patients. In recent years, TNF antagonists have been used to treat autoimmune diseases (AD) and provide better symptom control and quality of life for these individuals. However, during the chronic phase of toxoplasmosis, IFN-γ and its receptor, IFN-γR, also need the action of TNF-α and TNFR to maintain disease resistance and latency, and several studies have shown risk of reactivation of latent infections, including toxoplasmosis, in patients with AD using immunomodulators, due to the decreased surveillance of these cytokines.. In the present study, the objective was to verify whether patients with autoimmune diseases and using TNF antagonists have any indication of an increased risk of toxoplasmosis reactivation. For this purpose, peripheral blood samples were collected from patients who had already had contact with Toxoplasma gondii (IgG+), in addition to autoimmune diseases who were using synthetic (DS) and/or immunobiological drugs (IB) and from individuals in the control group (CG). Peripheral blood mononuclear cells were separated and evaluated after stimulation with total antigens free of Toxoplasma gondii and with anti-CD3 and anti-CD28 or without any stimulus, at 48 and 96 hours. The following markers were evaluated: CD69+ and CD28+ for activation and PD-1 for exhaustion; intracellular expression of IFN-γ, IL-17 and IL-10 by CD4+ and presence of regulatory CD4+ T cells by labeling CD25+, FOXP3 and LAP. The production of cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α and IL-17 was measured in culture supernatant after 96 hours. Serology for total IgG and IgG1 were also evaluated. It was observed that there was no difference in the levels of total IgG and IgG1 between the groups, but it was possible to observe that the IgG1 avidity was reduced in the IB compared to the CG. All groups showed a strong correlation between IgG and IgG1 positivity. Regarding cell analysis, it was seen that CD4+ T lymphocytes expressing PD-1 are increased in individuals with AD and using DMARDs. It was also verified that treatment with TNF blockers did not seem to influence the populations of regulatory T cells studied and did not interfere with the expression of the cytokines IFN-γ, IL-17 and IL-10 by CD4+ cells, nor with the production of cytokines by PBMCs from AD patients. Thus, we can conclude that apparently the use of immunobiologicals alone is not enough to unbalance immunity to the point of impairing the response to Toxoplasma gondii infection and predisposing to toxoplasmosis reactivation.