Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
Front Immunol. 2022 Aug 5;13:982186. doi: 10.3389/fimmu.2022.982186. eCollection 2022.
Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB104:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB104:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4 T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH.
自身免疫性肝炎（AIH）是一种由肝脏免疫稳态失调引起的自身免疫性疾病。遗传研究揭示了 AIH 与人类白细胞抗原（HLA）区域的易感性。最近，与基因组学相结合的代谢组学已经确定了许多具有生物医学意义的遗传位点。然而，AIH 中没有相关报道。在本研究中，我们发现 HLA-DRB104:05 与中国 AIH 患者的临床特征和预后相关。此外，我们将患者分为 DRB104:05 阳性和 DRB1*04:05 阴性两组，并通过 HPLC/MS 进行代谢组学分析。我们选择了肌苷这一高度改变的代谢物之一，来探讨其对急性重症肝炎小鼠模型的影响。结果表明，肌苷治疗可减轻肝细胞凋亡，增强抗氧化能力，并抑制 CD4 T 细胞的活化和糖酵解。我们提出，肌苷可能通过对肝细胞的保护作用和抑制过度激活的免疫细胞来参与 AIH 的调节，这可能为治疗急性 AIH 提供一种新的潜在方法。
