Pathogenesis of Autoimmune Hepatitis-Cellular and Molecular Mechanisms

• Published in: International journal of molecular sciences 2021-12, Vol.22 (24), p.13578
• Main Authors: Sirbe, Claudia, Simu, Gelu, Szabo, Iulia, Grama, Alina, Pop, Tudor Lucian
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antigens; Autoantibodies; Autoimmune diseases; Azathioprine; Azathioprine - therapeutic use; CD4 antigen; CD8 antigen; Cell division; Cholangitis; Chromatin; Clinical aspects; Cytotoxicity; Deoxyribonucleic acid; Disease; DNA; DNA methylation; DNA Methylation - drug effects; Epigenesis, Genetic - drug effects; Epigenetics; Etiology; Fibrosis; Gene expression; Genetic diversity; Glucocorticoids - therapeutic use; Hepatitis; Hepatitis, Autoimmune - drug therapy; Hepatitis, Autoimmune - genetics; Hepatitis, Autoimmune - immunology; Hepatitis, Autoimmune - pathology; Humans; Immunosuppressive Agents - therapeutic use; Laboratories; Liver; Liver - immunology; Liver - metabolism; Liver - pathology; Liver diseases; Lymphocytes; Lymphocytes B; Lymphocytes T; Mimicry; Molecular modelling; Nucleotide sequence; Pathogenesis; Pediatrics; Prednisolone; Prednisolone - therapeutic use; Proteins; Remission (Medicine); Review; RNA, Untranslated - genetics; RNA, Untranslated - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; Transcription; Transplantation; Transplants & implants
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222413578

Pediatric autoimmune liver disorders include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is an idiopathic disease characterized by immune-mediated hepatocyte injury associated with the destruction of liver cells, causing inflammation, liver failure, and fibrosis, typically associated with autoantibodies. The etiology of AIH is not entirely unraveled, but evidence supports an intricate interaction among genetic variants, environmental factors, and epigenetic modifications. The pathogenesis of AIH comprises the interaction between specific genetic traits and molecular mimicry for disease development, impaired immunoregulatory mechanisms, including CD4+ T cell population and Treg cells, alongside other contributory roles played by CD8+ cytotoxicity and autoantibody production by B cells. These findings delineate an intricate pathway that includes gene to gene and gene to environment interactions with various drugs, viral infections, and the complex microbiome. Epigenetics emphasizes gene expression through hereditary and reversible modifications of the chromatin architecture without interfering with the DNA sequence. These alterations comprise DNA methylation, histone transformations, and non-coding small (miRNA) and long (lncRNA) RNA transcriptions. The current first-line therapy comprises prednisolone plus azathioprine to induce clinical and biochemical remission. Further understanding of the cellular and molecular mechanisms encountered in AIH may depict their impact on clinical aspects, detect biomarkers, and guide toward novel, effective, and better-targeted therapies with fewer side effects.