Autoimmune hepatitis after liver transplantation and other lessons of self-intolerance.
Autoimmune hepatitis has been described as recurrent or de novo disease after transplantation. The legitimacy of these diagnoses and the bases for their occurrence are unknown. To better understand these aspects of allograft dysfunction, the purported pathogenic mechanisms of classical autoimmune hepatitis were reviewed and extrapolated to recurrent and de novo disease after transplantation. Loss of self-tolerance may relate to defects in the negative selection of autoreactive immunocytes and the clonal expansion of promiscuous lymphocytes that are cross-reactive to homologous antigens (molecular mimicry). Repopulation of the allograft with recipient antigen-presenting cells and the presence of primed promiscuous cytotoxic T cells within the recipient are likely factors for recurrent disease. Targets may be the same peptides that triggered the original disease, donor-derived class II antigens of the major histocompatibility complex, or homologous antigens associated with unidentified hepatotrophic viruses. De novo disease is probably due to similar mechanisms, but its predilection for children suggests that thymic dysfunction associated with cyclosporine treatment may be a factor. Corticosteroid therapy is effective in each condition. In conclusion, recurrent and de novo autoimmune hepatitis after transplantation are examples of self-intolerance. The mechanisms that perturb immunologic homeostasis in this human model of the classical disease must be studied more rigorously.
Czaja
Albert J
AJ
Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. czaja.albert@mayo.edu
D015551:Autoimmunity; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D019693:Hepatitis, Autoimmune / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D018716:Molecular Mimicry; D012008:Recurrence; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus