# Vitamin D binding protein (DBP) in innate immune cell response in viral myocarditis

> **NIH NIH R21** · MAYO CLINIC  JACKSONVILLE · 2022 · $18,925

## Abstract

PROJECT SUMMARY
Myocarditis caused by viral infections is a leading cause of sudden death in young adults and can progress to
dilated cardiomyopathy (DCM) and the need for a heart transplant. There is a clinical need to better
understand the mechanisms of the innate immune response underlying myocarditis in order to improve
diagnosis and prevent sudden death. Sex differences exist for most autoimmune and cardiovascular diseases.
Men have a higher incidence and severity of cardiovascular diseases including myocarditis/DCM than women.
In a proteomics study we found that serum vitamin D binding protein (DBP) and complement components were
upregulated in men with myocarditis compared to women, suggesting that sex differences in both DBP and
complement may increase cardiac inflammation in men. The activity and mechanism of DBP in innate immune
cells in myocarditis has not been previously investigated. In a highly translational preclinical animal model we
found that male mice deficient in DBP have significantly reduced inflammation and complement components
including C3 and C5/C5a compared to wild type controls indicating that DBP increases myocarditis in male
mice. This study examines whether sex differences in plasma DBP levels in patients with myocarditis correlate
to measures of heart failure like New York Heart Association Class, heart failure biomarkers, sex hormones
and/or complement components. We will further define the mechanisms whereby DBP increases the innate
immune system leading to increased cardiac inflammation using DBP deficient mice, C5a receptor antagonist
and C5a recombinant protein. We will additionally examine the effect of sex hormones on DBP and
complement components during viral myocarditis by looking at correlations between DBP, complement and
sex hormone levels. The successful completion of the study will significantly impact the field of myocarditis by
providing a mechanistic understanding of circulating DBP as a novel biomarker that may be used to predict the
risk of heart failure from myocarditis and determine whether therapies targeting DBP could reduce innate
immune cell recruitment and/or prevent myocarditis and sudden death.

## Key facts

- **NIH application ID:** 10435542
- **Project number:** 5R21AI163302-02
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Katelyn Ann Bruno
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $18,925
- **Award type:** 5
- **Project period:** 2021-06-22 → 2022-08-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435542

## Citation

> US National Institutes of Health, RePORTER application 10435542, Vitamin D binding protein (DBP) in innate immune cell response in viral myocarditis (5R21AI163302-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10435542. Licensed CC0.

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