# Identification of Anti-Neo-Antigen AutoAntibodies in Type 1 Diabetes

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2020 · $544,476

## Abstract

Identification of Anti-Neo-Antigen AutoAntibodies in Type 1 Diabetes
Abstract
 Type 1 diabetes (T1D) is an autoimmune disease characterized by the immunological destruction and
dysfunction of the insulin-producing pancreatic β-cells. One manifestation of the host's autoimmune response
is the production of T1D-specific autoantibodies (AAbs). These AAbs have become an important tool for T1D
research including their ability to predict and “stage” disease risk. However, despite extensive research efforts,
the mechanism(s) affording a breakdown of immune tolerance are still not fully understood. Furthermore, some
T1D patients are negative for the four known major AAbs at the time of diagnosis. It has recently been
postulated that an immune response to neo-antigens may represent an early event during T1D development.
Neo-antigens in this context arise from different mechanisms including protein isoforms translated from β-cell
specific transcripts as well as post-translationally modified proteins. Lessons from other autoimmune diseases
indicate their potential importance in T1D; however, there are only a few reports on T cell responses to
modified known major autoantigens. To our knowledge, there are few studies analyzing AAb responses to
neoantigens. We hypothesize that anti-neo-antigen autoantibodies (ANAAb) will be detectable in the
serum of recent-onset T1D patients. The completion of our proposed study will provide insight into the
role for ANAAbs in T1D development, identify candidate cellular immune response neo-antigens, offer
novel means for T1D risk prediction and patient stratification, provide potential antigenic candidates
for disease prevention trials, and improve our understanding of autoimmune destruction in this
disease. The lack of cost-effective high-throughput proteomics discovery platforms has, thus far, limited the
discovery of ANAAbs in T1D. Herein, we propose a novel means to identify ANAAbs in T1D by profiling serum
against thousands of T1D neoantigens on our contra capture protein array (CCPA) platform using samples
from recent-onset T1D patients and matched controls. HaloTagged proteins will be freshly expressed using a
HeLa cell based in vitro expression system, captured covalently onto the glass substrate coated with HaloTag
ligand, modified chemically or enzymatically, and profiled for sero-reactivity. We will utilize a two-stage
experimental design that includes discovery and blinded validation to reduce over fitting and ensure adequate
statistical power for an immunoproteomics study. Using replicate arrays displaying 2,000 proteins without
modification, with citrullination, deamidation, oxidization or carbamylation, T1D specific ANAAbs will be
discovered on NAPPA and validated by ELISA in a blind fashion with an independent set of samples. We will
perform epitope mapping for top ANAAb markers. We will also explore the potential pathophysiological roles of
these ANAAbs in T1D development and progression by assessing the ex...

## Key facts

- **NIH application ID:** 9993515
- **Project number:** 5R01DK120357-03
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** JOSHUA LABAER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $544,476
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993515

## Citation

> US National Institutes of Health, RePORTER application 9993515, Identification of Anti-Neo-Antigen AutoAntibodies in Type 1 Diabetes (5R01DK120357-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993515. Licensed CC0.

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