2nd Pediatric Discipline, Department of Mother and Child, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
2nd Pediatric Clinic, Center of Expertise in Pediatric Liver Rare Disorders, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania.
Int J Mol Sci. 2023 Apr 19;24(8):7479. doi: 10.3390/ijms24087479.
Autoimmune hepatitis (AIH) is characterized by immune-mediated hepatocyte injury resulting in the destruction of liver cells, causing inflammation, liver failure, and fibrosis. Pediatric (AIH) is an autoimmune inflammatory disease that usually requires immunosuppression for an extended period. Frequent relapses after treatment discontinuation demonstrate that current therapies do not control intrahepatic immune processes. This study describes targeted proteomic profiling data in patients with AIH and controls. A total of 92 inflammatory and 92 cardiometabolic plasma markers were assessed for (i) pediatric AIH versus controls, (ii) AIH type 1 versus type 2, (iii) AIH and AIH-autoimmune sclerosing cholangitis overlapping syndrome and (iv) correlations with circulating vitamin D levels in AIH. A total of 16 proteins showed a nominally significant differential abundance in pediatric patients with AIH compared to controls. No clustering of AIH subphenotypes based on all protein data was observed, and no significant correlation of vitamin D levels was observed for the identified proteins. The proteins that showed variable expression include CA1, CA3, GAS6, FCGR2A, 4E-BP1 and CCL19, which may serve as potential biomarkers for patients with AIH. CX3CL1, CXCL10, CCL23, CSF1 and CCL19 showed homology to one another and may be coexpressed in AIH. CXCL10 seems to be the central intermediary link for the listed proteins. These proteins were involved in relevant mechanistic pathways for liver diseases and immune processes in AIH pathogenesis. This is the first report on the proteomic profile of pediatric AIH. The identified markers could potentially lead to new diagnostic and therapeutic tools. Nevertheless, considering the complex pathogenesis of AIH, more extensive studies are warranted to replicate and validate the present study's findings.
自身免疫性肝炎 (AIH) 的特征是免疫介导的肝细胞损伤导致肝细胞破坏,引起炎症、肝衰竭和纤维化。儿科 AIH 是一种自身免疫性炎症性疾病,通常需要长期免疫抑制治疗。治疗停止后频繁复发表明,目前的治疗方法不能控制肝内免疫过程。本研究描述了 AIH 患者和对照者的靶向蛋白质组学分析数据。共评估了 92 种炎症和 92 种心血管代谢血浆标志物,用于 (i) 儿科 AIH 与对照者,(ii) AIH 1 型与 2 型,(iii) AIH 和 AIH-自身免疫性硬化性胆管炎重叠综合征,以及 (iv) AIH 中与循环维生素 D 水平的相关性。与对照组相比,儿科 AIH 患者共有 16 种蛋白质的丰度存在显著差异。基于所有蛋白质数据,未观察到 AIH 亚表型聚类,也未观察到鉴定出的蛋白质与维生素 D 水平有显著相关性。表现出可变表达的蛋白质包括 CA1、CA3、GAS6、FCGR2A、4E-BP1 和 CCL19,它们可能作为 AIH 患者的潜在生物标志物。CX3CL1、CXCL10、CCL23、CSF1 和 CCL19 彼此同源,可能在 AIH 中共同表达。CXCL10 似乎是列出的蛋白质的中心中间环节。这些蛋白质参与了 AIH 发病机制中肝脏疾病和免疫过程的相关机制途径。这是儿科 AIH 蛋白质组学特征的首次报告。鉴定出的标志物可能会带来新的诊断和治疗工具。然而,考虑到 AIH 的复杂发病机制,需要进行更广泛的研究来复制和验证本研究的发现。