Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
Division of Gastroenterology, Department of Internal Medicine, Fuji City General Hospital, Shizuoka, Japan.
BMJ Open Gastroenterol. 2022 Apr;9(1). doi: 10.1136/bmjgast-2022-000879.
MicroRNAs (miRNAs) are implicated in the pathogenesis of autoimmune diseases and could be biomarkers of disease activity. This study aimed to identify highly expressed circulating miRNAs in patients with autoimmune hepatitis (AIH) and to evaluate their association with clinical characteristics.
Microarray analyses were performed, and miRNA expression profiling for AIH, primary biliary cholangitis (PBC) and overlap syndrome (OS) using the serum of patients and healthy individuals was done. Samples were divided into discovery and test sets to identify candidate miRNAs that could discriminate AIH from PBC; the former included 21 AIH and 23 PBC samples, while the latter included five AIH and eight PBC samples.
Among 11 candidate miRNAs extracted in the discovery set, 4 (miR-3196, miR-6125, miR-4725-3 p and miR-4634) were specifically and highly expressed in patients with AIH in the test set. These four miRNAs discriminated AIH from PBC with high sensitivity (0.80-1.00) and specificity (0.88-1.00). In situ hybridisation analysis revealed that these miRNAs were expressed in the cytoplasm of hepatocytes in patients with AIH. Their expression levels were highest in untreated patients with AIH, followed by those in untreated patients with OS. They drastically or moderately decreased after prednisolone treatment. Histological analysis demonstrated that the expression levels of miR-3196, miR-6125 and miR-4634 in patients with AIH and OS were correlated with severe hepatic necroinflammatory activity.
These circulating miRNAs are suggested to reflect hepatic necroinflammatory activity and serve as AIH-related and treatment-responsive biomarkers. These miRNAs could be beneficial in developing new therapeutic strategies for AIH.
MicroRNAs（miRNAs）参与自身免疫性疾病的发病机制，可能是疾病活动的生物标志物。本研究旨在鉴定自身免疫性肝炎（AIH）患者中高表达的循环 miRNA，并评估其与临床特征的关系。
进行了微阵列分析，并使用患者和健康个体的血清进行了 AIH、原发性胆汁性胆管炎（PBC）和重叠综合征（OS）的 miRNA 表达谱分析。样本分为发现和测试集，以鉴定能够区分 AIH 与 PBC 的候选 miRNA；前者包括 21 例 AIH 和 23 例 PBC 样本，后者包括 5 例 AIH 和 8 例 PBC 样本。
在发现集中提取的 11 个候选 miRNA 中，有 4 个（miR-3196、miR-6125、miR-4725-3p 和 miR-4634）在测试集中特异性和高度表达于 AIH 患者。这四个 miRNA 具有高灵敏度（0.80-1.00）和特异性（0.88-1.00），可区分 AIH 与 PBC。原位杂交分析显示，这些 miRNA 表达于 AIH 患者肝细胞的细胞质中。它们在未经治疗的 AIH 患者中的表达水平最高，其次是未经治疗的 OS 患者。经泼尼松龙治疗后，其表达水平急剧或中度下降。组织学分析表明，miR-3196、miR-6125 和 miR-4634 在 AIH 和 OS 患者中的表达水平与严重的肝坏死性炎症活动相关。
这些循环 miRNA 提示反映肝坏死性炎症活动，作为 AIH 相关和治疗反应的生物标志物。这些 miRNA可能有助于开发 AIH 的新治疗策略。
