# Biomarking IBD patient-specific disease features using the epithelial antigenic peptidome

> **NIH NIH R21** · CEDARS-SINAI MEDICAL CENTER · 2021 · $208,750

## Abstract

Project Summary/Abstract
 In immune-mediated diseases such as type1 diabetes, target-cell autoantibodies have
emerged as important clinical biomarkers of pre-clinical disease progression and mechanistic
disease subsets. However, with the focus on genetics, inflammatory effectors, and microbiome,
there has not been a modern search for such antibody biomarkers and the potential contribution
of anti-epithelial autoimmunity in IBD. This project tests the hypothesis that ulcerative colitis
phenotypes are distinguished by autoantibodies to mucosal epithelial proteins, addressed in two
aims.
 In the first aim, we apply the innovative peptide expression display (PED) technology to
display and analyze the antigenic epithelial peptidome. This includes bioinformatically
determining a comprehensive tabulation of human proteins with high likelihood for antigenicity
and ileal-colonic epithelial expression; and, representing these proteins as tiled peptide epitopes
with linked cognate oligonucleotides suitable for NGS-based identification and quantitation.
 In the second aim, we will assess archival sera of 654 well-characterized colonic IBD
patients and non-IBD controls to quantitate individual profiles of epithelial protein binding in
relation to two outcomes of ulcerative colitis (UC). The significance of the project has been
endorsed by the IBD Genetics Consortium (IBDGC), which made the UC colectomy cohort a
research priority, and will collaborate with this R21 via archival serum samples and associated
genetics and clinical metadata from the consortium UC patients and controls. Our primary study
will compare 300 UC subjects, equally divided into severe and mild phenotypes of outcome based
on time to colectomy. Our secondary study will compare 154 UC post-colectomy pouch patients,
divided into severe and absent pouchitis phenotypes. We will also study two age-matched
reference populations. Bioinformatic analyses will test for shared peptide specificities associated
with disease state (UC vs. non-IBD controls) and each of the two extreme phenotypes (severe
vs. mild UC; chronic pouchitis vs. late non-pouchitis). We also will perform exploratory tests for
the role of IBD predictive risk scores and select genetic loci on autoantibody specificities.
 If successful, this project will establish feasibility for the hypothesis, and foundational
targets to pursue mechanistic and clinical biomarker studies that may validate and refine its
implications for IBD pathogenesis and clinical applications.

## Key facts

- **NIH application ID:** 10261547
- **Project number:** 5R21DK127189-02
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** JONATHAN BRAUN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $208,750
- **Award type:** 5
- **Project period:** 2020-09-11 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261547

## Citation

> US National Institutes of Health, RePORTER application 10261547, Biomarking IBD patient-specific disease features using the epithelial antigenic peptidome (5R21DK127189-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10261547. Licensed CC0.

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