# ENBA2 in the pathogenesis of Sjogren's Syndrome

> **NIH NIH R21** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $189,000

## Abstract

Sjögren's syndrome is a chronic, rheumatic, autoimmune disease that is characterized by a lymphocytic
infiltrate of the exocrine glands as well as autoantibodies in the serum (anti-Ro/La or anti-SSA/SSB). Salivary
and lacrimal gland dysfunction leads to severe dry eyes and dry mouth (sicca) in almost all patients, while
some also have systemic (extra-glandular) manifestations that can involve the skin, lungs, kidneys, peripheral
nervous system, muscles, CNS or joints. There is no known effective disease-modifying therapy, so treatment
is symptomatic. Pathogenesis of the disease is poorly understood but involves a genetic risk as well as
environmental factors. Epstein Barr virus (EBV), a near ubiquitous human infection, has been implicated in
Sjögren's syndrome by several lines of evidence but a mechanism by which EBV might mediate pathogenesis
has not been demonstrated. A recent study found that Epstein Barr nuclear antigen 2 (EBNA2), a viral
transcription factor, preferentially binds genetics intervals containing a risk gene for systemic lupus
erythematosus. This disease is highly related to Sjögren's, including a substantial overlap of the respective
genetic associations. Binding to these lupus genomic areas was stronger when the interval contained the risk
allele of the associated single nucleotide polymorphism. Thus, our central hypothesis is that EBNA2
expression and its binding of gene promoter regions containing Sjögren's-associated single nucleotide
polymorphisms is a critical factor in the pathogenesis of Sjögren's syndrome. We will test this hypothesis by
determining whether EBNA2 tends to bind genetic intervals with Sjögren's risk genes by use of novel search
and analysis strategies. In addition we will determine whether EBNA2 is expressed more commonly in
Sjögren's salivary glands compared to glands from subjects without Sjögren's syndrome. The second set of
studies will use single cell transcriptome profiling from salivary gland frozen sections. This approach will find
changes in gene expression associated with EBNA2 expression. Thus, we will leverage our repository of more
than 1000 minor salivary gland biopsy specimens tied to extensive clinical and laboratory data for this project.
This project also takes advantage of the opportunity afforded when studying Sjögren's to easily access the
involved tissue; namely, salivary gland.

## Key facts

- **NIH application ID:** 9877198
- **Project number:** 1R21DE029303-01
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Robert Hal Scofield
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,000
- **Award type:** 1
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877198

## Citation

> US National Institutes of Health, RePORTER application 9877198, ENBA2 in the pathogenesis of Sjogren's Syndrome (1R21DE029303-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9877198. Licensed CC0.

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