# Whole Protein Arrays to Detect Antimicrobial Antibodies Associated with Triggering and Progression of Islet Autoimmunity in TEDDY

> **NIH NIH R01** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2024 · $1,449,016

## Abstract

Abstract
Type 1 diabetes (T1D) is a multifactorial disease caused by a complex interplay of genetic and environmental
factors. The genes that mediate disease susceptibility have largely been discovered. The importance of
environmental factors is widely acknowledged but their identification has been challenging. Virus infections have
long been among the prime candidates, but progress has been hindered by the narrow “candidate microbe”
approach and limited availability of large prospective studies. The present study fills this major knowledge gap
by combining the tremendous power of modern immunoproteomics technologies to detect antibodies against a
wide range of different microbes with world largest prospective birth cohort study evaluating the role of
environmental factors in the pathogenesis of T1D (the TEDDY study). The goal is to obtain a comprehensive
and holistic picture on microbial infections which are associated with increased or decreased risk of islet
autoimmunity (IA) and T1D. This goal directly addresses the founding aims of the TEDDY study. We have
assembled a highly integrative multi-disciplinary team with synergizing expertise in T1D, immunoproteomics,
high throughput arrays, virus diseases, metagenomics, virome analyses and advanced statistics. We use three
supplementary high-throughput arrays with full proteins as antigens to enable the detection of antibody
responses against both structural and linear antigen epitopes to increase the screening sensitivity. First, the
highest protein capacity Nucleic Acid Programmable Protein Array (NAPPA) technology is used to carry out a
wide screening of antibodies against 2000 different whole microbial proteins representing 171 viruses, bacteria,
and parasites selected specifically for their relevance to T1D at a critical time-point of T1D pathogenesis, the
serum sample where IA was first detected (600 TEDDY IA+ children and 600 matched control children); Second,
the quantitative Multiplexed In-Solution Protein Array (MISPA) technology is used to identify infections and their
timing in childhood by analyzing antibodies to 400 best microbial protein candidates selected based on Aim 1
results from all prospective serum samples from infancy through IA (the same 600 cases plus 1200 HLA matched
controls at ~7 time points ≈ 12,600 samples). Third, widely used commercial Meso Scale Discovery (MSD) and
other technologies are employed to confirm the microbe-IA associations observed on the MISPA platform (the
same cohort as used on MISPA plus additional samples after the initiation of IA to study accelerants of
progression to clinical T1D). Overall, the results from this well-powered study will shape the landscape in this
field as this study represents the largest and widest screening of infections in children who develop IA/T1D. This
information is not only crucial for the understanding of T1D pathogenesis and for opening new possibilities to
prevent and treat the disease by vaccines or other antimicr...

## Key facts

- **NIH application ID:** 10975186
- **Project number:** 1R01DK140781-01
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** William A. Hagopian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,449,016
- **Award type:** 1
- **Project period:** 2024-09-05 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975186

## Citation

> US National Institutes of Health, RePORTER application 10975186, Whole Protein Arrays to Detect Antimicrobial Antibodies Associated with Triggering and Progression of Islet Autoimmunity in TEDDY (1R01DK140781-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10975186. Licensed CC0.

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