TABLE 5.
Feasible site-specific molecular and cellular interventions in autoimmune hepatitis (AIH)
| Intervention | Intervention attributes | Challenges |
|---|---|---|
| Monoclonal antibodies to CD3 | Nonmitogenic (7,12,14) Targets T cell antigen receptor (7,12,14) Promotes apoptosis, TGF-β release and regulatory T cell function (12,14) Effective in diabetic patients (7,12,14) |
Untried in AIH (12) Side effects (fever, anemia, rash, infection) (12) |
| Monoclonal antibodies to CD20 | Targets B lymphocytes (14) | Intravenous infusion required (89) |
| Prevents autoantibody production and antibody-dependent cytotoxicity (14) | Leukoencephalopathy (14) | |
| Limits cytokine production, antigen presentation, and T cell activation (14) | Interstitial pneumonitis (14) | |
| Limited trials in AIH (14,62,89) | Virus reactivation (14) | |
| Bacterial infections (14) | ||
| Recombinant CTLA-4Ig | Blocks second costimulatory T cell signal (12,14) | Untried in AIH (3,2,14) |
| Approved for rheumatoid arthritis (12,14) | ||
| Effective in animal model of primary biliary cirrhosis (90) | ||
| Adoptive transfer of regulatory T cells | Modulate immune response (12,14) Generate and maintain in cell culture (94) Success in animal model of AIH (93) |
Uncertain pathogenic mechanisms (correct T cell deficiencies or bolster effect) (91,92) |
| Tailored glycolipid antigen stimulation of natural killer T cells | Customized antigenic stimulation (96) | Untried in AIH (14) |
| Modulate immune response (95) | Uncertain disease specificity (14) | |
| Effective in other immune diseases (96–98) |
Numbers in parentheses refer to references. CTLA-4Ig Cytotoxic T cell antigen-4 fused with immunoglobulin; TGF-β Transforming growth factor-beta