Project Grant R21AI199336

Federal Grant Award Summary

The University of Texas Southwestern Medical Center received a $207,500 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded July 13, 2026, with completion targeted for June 30, 2028. This research initiative investigates the human genetics of severe autoimmune hepatitis (AIH) by analyzing next-generation sequencing data from two patient cohorts: 84 individuals with severe AIH enrolled through the Acute Liver Failure Study Group and 468 patients identified through the All of Us Research Program. The study integrates genomic and proteomic approaches to identify common and rare genetic risk factors contributing to disease severity, including analysis of genetic ancestry, human leukocyte antigen (HLA) genotypes, genome-wide association studies, and molecular characterization of novel risk variants.

Under Aim 2, the research team will conduct serum-based profiling to investigate the role of autoantibodies and circulating proteins in severe AIH using a bead-based multiplex autoantibody screening platform and targeted proteomic analysis via the Olink platform. Preliminary findings indicate significant enrichment of the HLA-DRB1*03 allele in severe AIH patients and identification of multiple candidate genes and autoantibodies as potential disease-causing or risk factors. The project aims to elucidate underlying immunogenetic mechanisms to advance understanding of AIH severity and inform future therapeutic strategies.