TABLE 2.
Future feasible drug alternatives for autoimmune hepatitis (AIH)
| Feasible molecular intervention | Mechanisms of action (reference[s]) | Precedents in human diseases (reference[s]) |
|---|---|---|
| Nonmitogenic monoclonal antibodies to CD3 (anti-CD3) | Targets T cell antigen receptor (17,55) | Type 1 diabetes (17,55) |
| Induces apoptosis of lymphocytes (17) | Few side effects (fever, rash, anemia, EBV infection) (17) | |
| Releases TGF-β (17) | ||
| Induces regulatory T cells (17) | ||
| Suppresses immune response (17) | ||
| Monoclonal antibodies to CD20 (anti-CD20) | Targets CD20 expressed on B cells (17) | Hematological malignancies (17) |
| Depletes B lymphocytes (17) | Rheumatoid arthritis, ITP (17) | |
| Impairs type 2 cytokine pathway (17) | AIH and cryoglobulinemia (17) | |
| Interferes with antibody-dependent cell-mediated cytotoxcities (17) | AIH and B cell lymphoma (17) | |
| Rare serious toxicities (progressive multifocal leukoencephalopathy) (17) | ||
| Monoclonal antibodies to TNF-α (anti-TNF-α) or its receptor (etanercept) | Interferes with type 1 cytokine pathway (15–17) | Crohn disease (16,17) |
| Impairs proliferation of cytotoxic T cells (15–17) | Rheumatoid arthritis (16,17) | |
| Alcoholic hepatitis (ineffective) (16,17) | ||
| NAFLD (ineffective) (16,17) | ||
| Serious toxicities (infection, death, lung disease, SLE, AIH) (16,17) | ||
| Recombinant cytotoxic T lymphocyte antigen 4 fused with immunoglobulin | Resembles CD28 on lymphocyte (15–17) | Rheumatoid arthritis (15–17) |
| Binds B7 ligands on APC (15–17) | Mismatched bone marrow transplantation (15–17) | |
| Interferes with second costimulatory signal of lymphocyte activation (15–17) | Multiple sclerosis (15–17) | |
| Few side effects (infection) (16,17) | ||
| Recombinant interleukin-10 | Counters type 2 cytokine path (15–17) | Chronic hepatitis C (15–17) |
| Reduces TNF-α (15–17) | Inflammatory bowel disease (15–17) | |
| Decreases inflammation (15–17) | Few dose-related side effects (anemia, thrombocytopenia, fever, chills, myalgias, headache) (16,17) | |
| Impairs differentiation and proliferation of T lymphocytes (15–17) |
Numbers in parentheses indicate reference(s). APC Antigen presenting cell; EBV Epstein-Barr virus; ITP Idiopathic thrombocytopenic purpura; NAFLD Nonalcoholic fatty liver disease; SLE Systemic lupus erythematosus; TNF-α Tumour necrosis factor-alpha; TGF-β Transforming growth factor-beta