Immunogenetic Profiling for Risk of Primary Graft Dysfunction after Heart Transplantation

NIH RePORTER · NIH · R21 · $201,250 · view on reporter.nih.gov ↗

Abstract

Immunogenetic Profiling for Risk of Primary Graft Dysfunction after Heart Transplantation For the approximately 250,000 people in the United States living with end-stage heart failure, heart transplantation (HT) remains the gold standard therapy. Despite excellent long-term survival, early mortality remains high as a result of infection, rejection, and primary graft dysfunction (PGD). PGD, in particular, is a devastating complication of HT in which acute failure of the new allograft leads to hemodynamic instability and end-organ hypoperfusion. Thus, we propose herein to build upon interesting preliminary data suggesting that plasma levels of CLEC4C, a protein that serves as a cell surface receptor for plasmacytoid dendritic cells (pDCs), are higher prior to transplant in patients who subsequently develop PGD after HT. Specifically, we will integrate immune profiling, single cell sequencing of pDCs and PBMCs, and single cell proteomics in isolated pDCs to test the hypothesis that pDCS are quantitatively and functionally enriched in HT recipient who develop PGD. This study has the potential to identify clinically relevant biomarkers in the care of HT recipients and may help to elucidate the underlying molecular mechanisms of PGD.

Key facts

NIH application ID
10391731
Project number
1R21AI167366-01
Recipient
DUKE UNIVERSITY
Principal Investigator
Svati H. Shah
Activity code
R21
Funding institute
NIH
Fiscal year
2022
Award amount
$201,250
Award type
1
Project period
2021-11-01 → 2023-10-31