# Autoimmune Mechanisms in Human Myocarditis

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $581,699

## Abstract

Myocarditis may be caused by a viral infection of the heart which may lead to a more chronic heart disease
often referred to as dilated cardiomyopathy (DCM). Myocarditis may lead to heart failure or a weakened heart
muscle requiring a heart transplant for survival. We have discovered a new myocarditis phenotype which
correlates with disease progression, non-recovery, and heart failure in human myocarditis and we have
linked it to innate and adaptive immune responses against cardiac myosin. Human cardiac myosin (HCM) we
found to be a novel damage associated molecular pattern or DAMP which interacts with TLR2 and stimulates
human CD14+ monocytes. The specific aims proposed will be a significant step forward in understanding
human myocarditis and may identify genes and pathways involved in disease progression. We expect to
identify predictors of myocarditis progression to heart failure and non-recovery and to identify potential
therapeutic interventions which can be instituted before inflammation leads to disease progression. While
most studies of myocarditis/DCM are in animal models, our project proposes innovative translational research
in a longitudinal study of a human myocarditis cohort to: Aim 1) Determine blood and heart biopsy
immunophenotypes of human myocarditis and identify novel upregulated genes and pathways which
associate with heart failure in myocarditis phenotypes by identification of the pro-fibrotic transcriptome of
CD4+ T cells in human myocarditis vs normal controls by RNAseq analysis; Aim 2) Identify T cell epitopes
of HCM in human myocarditis using state of the art HLA-epitope discovery combined with traditional T cell
epitope mapping of T cell clones using our human cardiac myosin peptide libraries; Aim 3) Identify the
upregulated genes and transcriptome of pro-fibrotic CD14+ monocyte responses against HCM toll like
receptor ligands that may lead to identification of pro-fibrotic and novel genes involved in progression of
myocarditis. RNAseq analysis of purified cell types such as CD14+ monocytes and CD4+ T cells will provide
insight into novel genes and pathways involved in pathogenesis so that future experiments can investigate
these new pathways. We expect that our studies using state of the art epitope discovery utilizing mass spec
to identify eluted human HLA bound peptides of HCM combined with more traditional epitope mapping using
T cell clones and ELISPOT will reveal epitopes and potential targets for immunotherapy. The RNAseq is
expected to reveal genes and pathways showing the critical role of monocytes and human cardiac myosin in
controlling myocarditis not previously recognized in humans. Most importantly, the phenotypes and
upregulated gene pathways will be correlated with outcomes such as heart function and fibrosis in our
myocarditis/DCM cohort. The proposed studies in humans will establish myocarditis immunophenotypes (T
cell and monocyte) which control outcomes in myocarditis/DCM and correlate individual phen...

## Key facts

- **NIH application ID:** 10098332
- **Project number:** 5R01HL135165-05
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** LESLIE T COOPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $581,699
- **Award type:** 5
- **Project period:** 2017-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098332

## Citation

> US National Institutes of Health, RePORTER application 10098332, Autoimmune Mechanisms in Human Myocarditis (5R01HL135165-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10098332. Licensed CC0.

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