Emerging Opportunities for Site-Specific Molecular and Cellular Interventions in Autoimmune Hepatitis

Abstract

Current corticosteroid-based treatments of autoimmune hepatitis frequently have incomplete or unsatisfactory outcomes, side effects, and excessive immune suppression. The goal of this review is to describe the advances in developing animal models of autoimmune hepatitis and in treating diverse immune-mediated diseases that make pursuit of site-specific molecular and cellular inventions in autoimmune hepatitis feasible. Prime source and review articles in English were selected by a Medline search through October 2009. A murine model infected with an adenovirus expressing human CYP2D6 is a resource for evaluating new therapies because of its histological and serological features, persistence, and progressive hepatic fibrosis. Synthetic analog peptides that block autoantigen expression, a dimeric recombinant human fusion protein of cytotoxic T lymphocyte antigen-4, monoclonal antibodies against tumor necrosis factor-alpha, recombinant interleukin 10, tolerization techniques for disease-triggering autoantigens, T regulatory cell transfer, vaccination against antigen-specific cytotoxic CD8+ T cells, and gene silencing methods using small inhibitory RNAs are feasible interventions to explore. Treatments directed at dampening immunocyte activation with soluble cytotoxic T lymphocyte antigen-4, inhibiting immunocyte differentiation with recombinant interleukin 10, and improving immunosuppressive activity with regulatory T cell modulation have the most immediate promise. Progress in the development of an animal model of autoimmune hepatitis and experiences in other immune-mediated diseases justify the evaluation of site-specific molecular and cellular interventions in this disease.