Retired, Rochester, MN, United States.
Front Immunol. 2022 Jun 30;13:921765. doi: 10.3389/fimmu.2022.921765. eCollection 2022.
The observed risk of autoimmune hepatitis exceeds its genetic risk, and epigenetic factors that alter gene expression without changing nucleotide sequence may help explain the disparity. Key objectives of this review are to describe the epigenetic modifications that affect gene expression, discuss how they can affect autoimmune hepatitis, and indicate prospects for improved management. Multiple hypo-methylated genes have been described in the CD4 and CD19 T lymphocytes of patients with autoimmune hepatitis, and the circulating micro-ribonucleic acids, miR-21 and miR-122, have correlated with laboratory and histological features of liver inflammation. Both epigenetic agents have also correlated inversely with the stage of liver fibrosis. The reduced hepatic concentration of miR-122 in cirrhosis suggests that its deficiency may de-repress the pro-fibrotic . Conversely, miR-155 is over-expressed in the liver tissue of patients with autoimmune hepatitis, and it may signify active immune-mediated liver injury. Different epigenetic findings have been described in diverse autoimmune and non-autoimmune liver diseases, and these changes may have disease-specificity. They may also be responses to environmental cues or heritable adaptations that distinguish the diseases. Advances in epigenetic editing and methods for blocking micro-ribonucleic acids have improved opportunities to prove causality and develop site-specific, therapeutic interventions. In conclusion, the role of epigenetics in affecting the risk, clinical phenotype, and outcome of autoimmune hepatitis is under-evaluated. Full definition of the epigenome of autoimmune hepatitis promises to enhance understanding of pathogenic mechanisms and satisfy the unmet clinical need to improve therapy for refractory disease.
观察到的自身免疫性肝炎的风险超过了其遗传风险，而改变基因表达但不改变核苷酸序列的表观遗传因素可能有助于解释这种差异。本文的主要目的是描述影响基因表达的表观遗传修饰，讨论它们如何影响自身免疫性肝炎，并指出改善管理的前景。在自身免疫性肝炎患者的 CD4 和 CD19 T 淋巴细胞中已经描述了多个低甲基化基因，循环 microRNA（miR-21 和 miR-122）与肝炎症的实验室和组织学特征相关。两种表观遗传药物也与肝纤维化的分期呈负相关。肝硬化中 miR-122 的肝浓度降低表明其缺乏可能会抑制促纤维化。相反，miR-155 在自身免疫性肝炎患者的肝组织中过度表达，它可能表明存在活跃的免疫介导的肝损伤。在不同的自身免疫性和非自身免疫性肝病中已经描述了不同的表观遗传发现，这些变化可能具有疾病特异性。它们也可能是对环境线索或区分这些疾病的可遗传适应的反应。表观遗传编辑和 microRNA 阻断方法的进步提高了证明因果关系和开发针对特定部位的治疗干预措施的机会。总之，表观遗传学在影响自身免疫性肝炎的风险、临床表型和结局方面的作用尚未得到充分评估。自身免疫性肝炎的表观基因组的全面定义有望增强对发病机制的理解，并满足改善难治性疾病治疗的未满足的临床需求。
