# A Multiomic Search for Antigens in Autoimmune Hepatitis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $201,875

## Abstract

Abstract/Project Summary
Autoimmune hepatitis (AIH) is traditionally viewed as rare and of unclear etiology. More than 70 years since its
first description, nonspecific immunosuppression with corticosteroids remains the cornerstone of therapy. Like
other autoimmune disorders, recent data suggest that AIH may be rising in incidence and prevalence. Our
group has shown that AIH not only disproportionately affects women but also people of color, both among San
Francisco’s underserved population and nationally in terms of hospitalizations for AIH. In order to understand
these disparities, we have developed collaborations to study biologic mechanisms underlying AIH. With
funding from the American Association for the Study of Liver Diseases, we performed transcriptomic analysis
of whole blood samples from AIH patients and controls at Indiana University. The blood of AIH patients was
notable for activation of interferon signaling and the presence of pegivirus in several samples. Molecular
mimicry has been proposed as a mechanism of AIH pathogenesis, e.g. exposure to a viral antigen may result
in aberrant immune recognition of structurally similar antigens in the liver. While the autoantigen for the rarer
Type 2 AIH has been identified, no autoantigen has been identified in the more commonly encountered Type 1
AIH. Our collaborators have developed a system for identifying human and viral antigens called Phage
Immunoprecipitation-Sequencing (PhIP-Seq). In an ongoing study Prospective Observational Study to
Understand Liver Diseases (POSULD), we have been collecting clinical data and biospecimens from AIH
patients and controls at UCSF. Preliminary analysis of a small number of POSULD samples by PhIP-Seq
identified six potential autoantigens for AIH. These data suggest that analysis of more samples from racially
and ethnically diverse patients with AIH and controls could lead to the identification of an autoantigen or
autoantigens and clarify the etiopathogenesis of this enigmatic disease. Given these findings, we hypothesize
that there is a heretofore unidentified hepatic autoantigen in Type 1 AIH, which may be structurally similar to a
viral antigen. This hypothesis will be addressed in the following Specific Aims: (1) To determine human
autoantigens in patients with Type 1 AIH; and (2) To investigate viral antigens in patients with Type 1 AIH and,
if any are found, assess their similarity to any human autoantigens found in Aim 1. Should this exploratory
study improve our understanding of AIH pathogenesis, the findings may provide insight into the health
disparities observed by our group and others. Furthermore, therapies aimed at treating or preventing viral
infection or modifying the immune response to said antigens may open new avenues of therapy for AIH.

## Key facts

- **NIH application ID:** 10107055
- **Project number:** 1R21DK127275-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Michele May-Sien Tana
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,875
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107055

## Citation

> US National Institutes of Health, RePORTER application 10107055, A Multiomic Search for Antigens in Autoimmune Hepatitis (1R21DK127275-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10107055. Licensed CC0.

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