Antigen-Specific Immunotherapy for Treatment of Autoimmune Liver Diseases

Abstract

The liver is a critical organ in controlling immune tolerance. In particular, it is now clear that targeting antigens for presentation by antigen presenting cells in the liver can induce immune tolerance to either autoantigens from the liver itself or tissues outside of the liver. Here we review immune mechanisms active within the liver that contribute both to the control of infectious diseases and tolerance to self-antigens. Despite its extraordinary capacity for tolerance induction, the liver remains a target organ for autoimmune diseases. In this review, we compare and contrast known autoimmune diseases of the liver. Currently patients tend to receive strong immunosuppressive treatments and, in many cases, these treatments are associated with deleterious side effects, including a significantly higher risk of infection and associated health complications. We propose that, in future, antigen-specific immunotherapies are adopted for treatment of liver autoimmune diseases in order to avoid such adverse effects. We describe various therapeutic approaches that either are in or close to the clinic, highlight their mechanism of action and assess their suitability for treatment of autoimmune liver diseases.

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer

“…The liver plays a key role in immune tolerance (8) and it hosts a rich, specialised immune compartment (9, 10). Regulatory T cells (Treg) play a critical role in dampening overactive immune responses (11,12).…”

Peptide allergen‐specific immunotherapy for allergic airway diseases—State of the art

“…27,28 This concept has been also been tested with some success in the context of autoimmune diseases where there are recognized target antigens such as in autoimmune liver diseases, rheumatoid arthritis, type-I diabetes, multiple sclerosis and Graves' disease. [28][29][30][31][32][33][34] Targeting pathogenic T cells in organ-specific autoimmune diseases with T cell epitopes induces antigen-specific regulatory T cells and this strategy is under evaluation in clinical trials.…”

“…Predefined and well‐mapped short peptides (SPs) or long COPs of major allergens representing dominant T cell epitopes, with the ability to bind to a vast array of HLA class II alleles, can be administered at regular intervals, either intradermally or subcutaneously to induce allergen‐specific T cell tolerance 27,28 . This concept has been also been tested with some success in the context of autoimmune diseases where there are recognized target antigens such as in autoimmune liver diseases, rheumatoid arthritis, type‐I diabetes, multiple sclerosis and Graves’ disease 28–34 . Targeting pathogenic T cells in organ‐specific autoimmune diseases with T cell epitopes induces antigen‐specific regulatory T cells and this strategy is under evaluation in clinical trials.…”

Classic Autoimmune Liver Disorders and Celiac Hepatitis

“…Cell‐mediated autoimmunity is evident in both AIH and PBC by the presence of self‐antigen‐specific T cells within the liver. Specific targets of cellular or humoral autoimmunity in PSC are not clear yet 2,7 . Quantity and immunosuppressive capacity of regulatory T cells (Tregs) are altered in AIH, PBC, and PSC 2,8,9 .…”