# Project 3-Proteomic Analysis of Explanted Livers with characterization of Autoantigens

> **NIH NIH P50** · JOHNS HOPKINS UNIVERSITY · 2020 · $303,112

## Abstract

PROJECT SUMMARY
Severe alcoholic hepatitis (SAH) is the most severe form of the alcoholic liver diseases (ALD). Chronic alcohol
abuse is associated with increased susceptibility to pneumonia, infections (e.g., HIV, HCV, and Tuberculosis),
and with chronic inflammation. Studies in the past thirty years in both humans and animal models revealed that
ALD is likely caused by impact of alcohol abuse on adaptive immune system. Chronic alcohol abuse was found
to reduce the number of B cells, decrease antigen-specific antibody responses, and increase the production of
autoantibodies against liver autoantigens and byproducts of oxidative damage. Moreover, increased levels of
immunoglobulin of IgG, IgA, and IgE isotypes and production of autoantibodies against liver antigens have
been observed in patients with SAH. Therefore, we hypothesize that generation of autoantibodies in patients
with SAH contributes to liver damage. To fully test this hypothesis, the identification of those antigens
recognized by antibodies deposited in SAH livers is a crucial stepping-stone towards understanding the
etiology of the diseases. In addition, it is likely that some of these antibodies are created from cross-reacting
antibodies directed against bacteria in the gut. The goal of this proposal is to determine the origins of these
SAH-specific antibodies in patients with SAH and characterize their function and contribution to liver damage.
We will take full advantage of the biospecimens collected from the explanted livers of patients with SAH, as
well as donor livers and livers diagnosed for other liver diseases, and employ the cutting-edge protein
microarray technology to achieve four Specific Aims: 1) Identify autoantigens that are specifically recognized
by antibodies extracted from explanted livers or blood of the patients with SAH; 2) Profile antibody signatures
to bacterial antigens in patients with SAH; 3) Characterize functions of the antibodies extracted from SAH livers
using a cell-based model; and 4) Examine whether alcohol abuse-induced autoantibodies cause liver allograft
injury in alcohol relapse patients after liver transplantation. We believe that of this project will allow us to
identify novel therapeutic targets and develop novel therapy for intervention and prevention of SAH.

## Key facts

- **NIH application ID:** 9852407
- **Project number:** 5P50AA027054-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Heng Zhu
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $303,112
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852407

## Citation

> US National Institutes of Health, RePORTER application 9852407, Project 3-Proteomic Analysis of Explanted Livers with characterization of Autoantigens (5P50AA027054-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852407. Licensed CC0.

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