Altered Immune Profiles in Non-Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy.

INTRODUCTION

Cardiac allograft vasculopathy (CAV) develops more aggressively in recipients of hearts from brain-dead (BD) donors with induced long QT syndrome (iLQTS), yet the underlying mechanisms remain poorly understood. In this study, we employ a multi-omics and experimental framework to explore the role of neuro-immune interactions in non-failing donor hearts affected by iLQTS.

METHODS

Single-nuclei RNA sequencing (snRNA-seq) compared four iLQTS and four non-arrhythmic non-failing donor hearts. Pathway enrichment and cell-cell communication were assessed. Plasma proteome data from BD donors and neuronal differentially expressed (DE) genes were integrated via Omicsnet. Human BD donor transcriptomes data were analyzed for immune correlation.

RESULTS

ILQTS hearts showed elevated T/mast cells and upregulated leukocyte migration/focal adhesion pathways. Neuronal signaling (NGF, HSPG) and adhesion molecules (ITGB1, LAMININ) drove immune trafficking. Integrative proteomics identified ITGB1 as a central hub linking neuronal DE genes to BD-associated plasma proteins. Human validation linked activated CD4 T cells/Th2 enrichment to prolonged QT intervals.

CONCLUSIONS

Neuro-immune dysregulation and integrin signaling related T cell activation underlie iLQTS-related heart donors. Targeting neuronal-integrin crosstalk may reduce CAV progression and improve transplant outcomes.