Andrade Cristhianne Molinero Ratkevicius, de Lima Marques Aline Caroline, Timóteo Rodolfo Pessato, de Morais Oliveira-Scussel Ana Carolina, De Vito Fernanda Bernadelli, da Silva Marcos Vinícius, Mineo José Roberto, Teodoro Reginaldo Botelho, Rodrigues Denise Bertulucci Rocha, Júnior Virmondes Rodrigues
Laboratory of Immunology, Triângulo Mineiro Federal University, Uberaba 38025-350, Brazil.
Laboratory of Hematological Research, Triângulo Mineiro Federal University, Uberaba 38025-350, Brazil.
Biomedicines. 2023 Mar 17;11(3):930. doi: 10.3390/biomedicines11030930.
(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 (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 , 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- immune response and predisposing to toxoplasmosis reactivation.
(1) 背景:肿瘤坏死因子拮抗剂已被用于治疗自身免疫性疾病(AD)。然而,在弓形虫病的慢性期,肿瘤坏死因子-α(TNF-α)和肿瘤坏死因子受体(TNFR)在维持疾病抵抗力和潜伏期方面发挥着重要作用。多项研究已证明感染弓形虫病的患者存在潜伏感染激活的风险。我们的目的是验证使用肿瘤坏死因子拮抗剂和/或合成药物且既往有弓形虫免疫球蛋白G(IgG)接触史的自身免疫性风湿病患者是否有任何弓形虫病激活风险增加的迹象。(2) 方法:采集血样,并用弓形虫抗原、抗CD3/抗CD28刺激外周血单个核细胞(PBMC),或不进行刺激,在48小时和96小时后进行评估。评估CD69、CD28和程序性死亡受体1(PD-1)染色,以及CD4细胞内γ干扰素(IFN-γ)、白细胞介素17(IL-17)和白细胞介素10(IL-10)的表达,通过标记CD25、叉头框蛋白P3(FOXP3)和肝细胞核因子4α(LAP)检测调节性CD4 T细胞的存在。96小时后测量培养上清液中的细胞因子白细胞介素2(IL-2)、白细胞介素4(IL-4)、白细胞介素6(IL-6)、白细胞介素10、IFN-γ、TNF-α和IL-17。评估IgG和IgG1的血清学。(3) 结果:各组之间IgG和IgG1水平无差异,但免疫生物学组的IgG1亲和力与对照组相比降低。所有组的IgG和IgG1阳性之间均存在显著相关性。在患有自身免疫性风湿病且使用改善病情抗风湿药物的个体中,表达PD-1的CD4 T淋巴细胞增加。此外,肿瘤坏死因子阻滞剂治疗似乎不影响调节性T细胞群体,也不干扰AD患者CD4细胞中IFN-γ、IL-17和IL-10细胞因子的表达或PBMC产生细胞因子。(4) 结论:本研究提供的证据表明,使用TNF-α阻滞剂不会导致免疫失衡,以至于损害抗免疫反应并易引发弓形虫病激活。