Emerging Serological Biomarkers for Autoimmune Hepatitis

Autoimmune hepatitis (AIH) lacks a disease-specific diagnostic biomarker, particularly for patients who present with acute onset, normal IgG levels, or seronegative profiles. Recent advances in high-throughput autoantibody profiling technologies have enabled the systematic discovery of novel AIH-associated autoantigens. This review summarizes emerging autoantibodies that have been identified through proteome-wide screening approaches, including human protein microarrays and phage immunoprecipitation sequencing. Particular attention is given to anti-docking protein 2 (DOK2) and anti-mitochondrial ribosomal protein S27 (MRPS27) antibodies, which have shown promising diagnostic performance. Importantly, the combined assessment of these autoantibodies markedly improves the diagnostic sensitivity for AIH and may be useful for screening or clinical triage, although its reduced specificity limits its use as a stand-alone confirmatory test. We also discuss how the integration of serological biomarkers with molecular pathology and spatial immune analysis may advance the understanding of AIH pathogenesis. These developments highlight the potential of proteome-wide autoantibody discovery to refine diagnostic strategies for AIH and provide new insights into disease mechanisms.