Melgaço Juliana Gil, Soriani Frederico Marianetti, Sucupira Pedro Henrique Ferreira, Pinheiro Leonardo Assaf, Vieira Yasmine Rangel, de Oliveira Jaqueline Mendes, Lewis-Ximenez Lia Laura, Araújo Cristina Carvalho Vianna, Pacheco-Moreira Lúcio Filgueiras, Menezes Gustavo Batista, Cruz Oswaldo Gonçalves, Vitral Claudia Lamarca, Pinto Marcelo Alves
Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
World J Hepatol. 2016 Nov 18;8(32):1370-1383. doi: 10.4254/wjh.v8.i32.1370.
To study the differences in immune response and cytokine profile between acute liver failure and self-limited acute hepatitis.
Forty-six patients with self-limited acute hepatitis (AH), sixteen patients with acute liver failure (ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced self-limited AH and ALF. Thus, we worked with five groups: Hepatitis A virus (HAV)-induced self-limited acute hepatitis (HAV-AH), HAV-induced ALF (HAV-ALF), non-viral-induced self-limited acute hepatitis (non-viral AH), non-viral-induced acute liver failure (non-viral ALF), and healthy subjects (HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.
The levels of mitochondrial DNA (mtDNA) and the cytokines investigated [interleukin (IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology ( < 0.05). High plasma mtDNA and IL-10 were the best markers associated with ALF [mtDNA: OR = 320.5 (95%CI: 14.42-7123.33), < 0.0001; and IL-10: OR = 18.8 (95%CI: 1.38-257.94), = 0.028] and death [mtDNA: OR = 12.1 (95%CI: 2.57-57.07), = 0.002; and IL-10: OR = 8.01 (95%CI: 1.26-50.97), = 0.027]. In the cellular proliferation assay, NK, NKT and regulatory T cells (TReg) predominated in virus-specific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature.
mtDNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.
研究急性肝衰竭与自限性急性肝炎在免疫反应和细胞因子谱方面的差异。
本研究纳入了46例自限性急性肝炎（AH）患者、16例急性肝衰竭（ALF）患者和22名健康受试者。使用商业酶联免疫吸附测定法和定量实时聚合酶链反应对血浆样本中的炎症和抗炎产物进行定量。通过流式细胞术增殖测定法测量细胞免疫反应。将这些组分为病毒诱导和非病毒诱导的自限性AH和ALF。因此，我们研究了五组：甲型肝炎病毒（HAV）诱导的自限性急性肝炎（HAV-AH）、HAV诱导的ALF（HAV-ALF）、非病毒诱导的自限性急性肝炎（非病毒AH）、非病毒诱导的急性肝衰竭（非病毒ALF）和健康受试者（HC）。对HAV诱导和非病毒诱导的AH及ALF进行了比较。
无论病因如何，ALF患者的线粒体DNA（mtDNA）水平以及所研究的细胞因子[白细胞介素（IL）-6、IL-8、IL-10、干扰素γ和肿瘤坏死因子]均显著升高（<0.05）。高血浆mtDNA和IL-10是与ALF相关的最佳标志物[mtDNA：OR = 320.5（95%CI：14.42 - 7123.33），<0.0001；IL-10：OR = 18.8（95%CI：1.38 - 257.94），= 0.028]以及与死亡相关的最佳标志物[mtDNA：OR = 12.1（95%CI：2.57 - 57.07），= 0.002；IL-10：OR = 8.01（95%CI：1.26 - 50.97），= 0.027]。在细胞增殖测定中，NK、NKT和调节性T细胞（TReg）在HAV诱导的ALF患者的病毒特异性刺激中占主导地位，其对有丝分裂刺激的细胞反应表现为无反应性。因此，在非病毒诱导的ALF中，如预期及文献所述，有丝分裂刺激后未观察到活化T细胞的无反应性行为。
mtDNA和IL-10可能是ALF和死亡的预测指标。TReg细胞参与了HAV诱导的ALF中的免疫紊乱。
