Year: 2026
Type: review
Abstract: Human leukocyte antigen (HLA) associations anchor genetic susceptibility to autoimmune hepatitis (AIH). Connecting this susceptibility to the immune reactions that sustain liver injury remains a central challenge. Recent antigen-specific experiments and tissue analyses provide complementary insights into recognition and injury. This Mini Review examines how population-specific HLA associations, SepSecS-reactive lymphocytes and intrahepatic immune states inform the relationship between antigen recognition and inflammatory amplification. The evidence reveals three unresolved relationships between susceptibility, recognition and injury. Class II-restricted autoreactivity and conditionally independent class I associations in Han Chinese AIH implicate potentially complementary immune pathways. Antigen-specific T-cell responses extend beyond the boundaries defined by autoantibody status. Receptor specificity and the capacity to sustain tissue injury require distinct functional tests. We evaluate antigen-presentation experiments, receptor studies and tissue profiling, distinguishing human observations from mechanistic models. The synthesis supports a model in which heterogeneous antigen-specific responses may converge on shared inflammatory processes. Priorities include linking genetic risk to natural antigen presentation and defining autoreactive clone function in liver tissue. Matched perturbation experiments should then test antigen dependence alongside cytokine-dependent injury. Resolving these questions would clarify which mechanisms require antigen-specific intervention and which reflect downstream inflammatory amplification.
Source: Frontiers in Immunology
Authors: Zihao Xu, Yifan Liu, Haoyang Zou, Sheng Guo
Language: English
Topic: Liver Diseases and Immunity
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222934992